00:07:20.24 And what Howard Green did in his breakthrough work to culture embryonic... to culture human Barely understood it. Part 2 00:00:17.02 I'm a professor at The Rockefeller University in New York City, 00:39:47.07 So, what about stem cell therapy for type I diabetes. It is made up of several layers of cells called keratinocytes. 00:16:24.11 And the slice of tissue that you're looking at is a mouse brain. This field is for validation purposes and should be left unchanged. 00:07:55.06 which also succeeded because of the addition of the fibroblast feeder layer. 00:23:32.23 So, this gets us over the hurdle. 00:00:44.20 It was only in 1877 that Ernst Haeckel, a German scientist, coined the word stammzelle, or stem cell, 00:14:32.12 TGF-beta or not. 00:01:23.26 He fled the Russian Revolution and joined the ranks of the University of Chicago. 00:09:34.10 The patient was near death at the point at which Michele De Luca, my colleague in Rome, 00:37:49.22 Well, the very first technology-driven therapy was for macular degeneration. 00:12:51.01 So, is this relevant? 00:23:29.09 and would be accepted by the person. 00:47:56.12 shown in gray, there's no epigenetic marks. 00:15:20.25 So, now we can treat the cells with cisplatin. 00:10:55.20 are called the trophectoderm. 00:20:46.02 And now the system returns back to normal again, to reset the hair cycle. 00:12:30.11 Scientists are excited about the ability to generate nerve cells for the treatment of 00:04:28.04 and the hairs of our body. 00:16:04.09 and the cells that can respond to TGF-beta are refractory. Common Name: {Fruit stem cell complex, lilac stem cells, phytocell tec malus domestica, apple stem cells, plant stem cells}. 00:34:46.06 So, in embryonic development, the skin begins as that single layer of epithelium and epidermal buds 00:38:33.24 If we switch them off, we can favor hair follicle tissue regeneration and hair regeneration. 00:23:26.21 epidermis and sebaceous glands. 00:21:47.25 And there's always that need to be able to draw parallels between mouse and human. 00:26:04.13 So, their transcriptional program reflects the behavior of these stem cells. 00:15:59.01 telling it to stay cool, be quiet, be dormant, and not make tissue. 00:11:48.04 It competes for the binding of KEAP1 to NRF2. 00:28:19.28 So, we understand how these different factors are working and how these different transcription factors... 00:27:27.20 to make a hair follicle, what we found to maintain the hair follicles stem cells... what we found 00:42:47.02 Cardiomyopathies. 00:09:30.26 and started to invade the stroma. 00:18:43.21 So, embryonic... embryos from in vitro fertilization are indeed often now discarded or frozen or 00:18:02.02 This is a problem that's faced by all the stem cells of our adult tissues. Green H, Kehinde O, Thomas J. 00:40:12.20 And they all bind to relatively short stretches of DNA that are contained within these large 00:10:40.06 And those are the cells that develop into the fetus, or the embryo. 00:12:11.15 There are many different cell types for which we don't have very much information, 00:12:07.01 And the ones that we identified that were up in the TGF-beta-responding stem cells The bulge stem cell is considered to be of higher hierarchy in terms of the stemness than the epidermal stem cell. 00:47:34.16 long after the inflammation has resolved. 00:34:14.21 But perhaps with a balance tempering those numbers of hair cycles, one might be able 00:11:54.06 just like, as I mentioned to you, epidermal stem cells were initially. 00:50:56.02 hyperinflammatory response, the barrier is at risk. 00:27:16.25 transcription factors the adult skin cell was making versus the embryonic stem cell and what kinds of 00:15:37.01 and die. 00:06:16.27 So, the epidermal stem cells could be grown for months in a dish, and forever when grafted 00:04:01.04 They'll also generate the corneal surface of our eye, the sweat glands, and the mammary glands. 00:01:44.00 Other tissues have very little regenerative capacity. 00:16:07.09 But these are the studies of Lorenz Studer, a scientist and one of my colleagues 00:22:28.06 They also produce epidermis and sebaceous glands. 00:05:03.27 but what we do know is that the phosphorylation and superactivation 00:40:32.18 coax these cells through individual steps, one by one, to be able to produce 00:40:08.14 and has made really remarkable advances in the course of these last twenty years. The epidermis and skin appendages need to be renewed constantly to keep your skin in good condition. 00:05:48.05 human epidermal stem cells. 00:16:24.11 which then go on to produce the bulk of the tissue. 00:30:17.19 for the SOX2, OCT4, KLF4, and cMyc genes are turned on after about 10 days of 00:13:46.26 So, let's take a look at a couple of examples of what embryonic stem cells can do. 00:28:28.13 So, let's put this all together now. 00:08:57.12 stem cells of the tumor in red. 00:03:23.04 of Till and McCullough, and now it wasn't until the mid 1970s when this person, 00:19:02.26 then, the stem cells are basically activated. 00:25:23.11 And then for a quiescent stem cell, the niche signals basically produce a gene expression profile 00:05:09.13 of these transcription factors is critical with regards to altered, 00:18:55.17 And so, again, this issue is, well, the embryos could be implanted into a woman who Oshimori N, Oristian D, Fuchs E. (2015) TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma. 00:14:19.01 Well, to this end, we've engineered isogenic strains, or isogenic cells, that contain This has been shown to be safe, but researchers are trying to develop methods that don’t require animal cells for treatments. 00:32:38.06 with regards to the length of their hair cycle. Nature.551(7680):327-332. 00:06:15.06 in the patient's bad skin. 00:46:09.26 now we see the activation of these enhancer elements. 00:17:17.23 that are located at the very base of the non-cycling portion of the hair follicle. 00:27:35.02 So in this way, we learned that TCF3 and 4 antagonize what Wnt signaling can do, MCB-1052331. 00:43:43.04 be used for activity screens for developing new drugs for the treatments of various different 00:42:08.04 for every stem cell type. 00:07:35.06 There are immune cells. 00:36:15.22 It doesn't spike in the body dermis, and therefore the animals get hair exclusively. 00:33:21.18 the need to introduce foreign genes or ectopic expression of genes into these cells. 00:37:43.11 So, are there clinical applications yet for iPS technology? 00:09:42.15 took on this task of working with German clinicians in order to be able to take a small sample 00:05:57.04 So, Howard Green went on to develop this technology for the treatment of burn patients, 00:15:07.28 into spinal cord neurons. 00:46:40.19 And that's a remarkable property, because, basically, this confers to the epidermal stem cells 00:19:09.16 And now the short-lived progeny may get a new signal, this one called sonic hedgehog. 00:04:54.07 So, Howard Green very soon recognized the power of the technology that he had just developed 00:32:41.21 Could he reduce the length of time that stem cells spend in quiescence? 00:30:57.11 Mayumi Ito and her coworkers, learned was that the melanocyte stem cells and 00:01:55.24 So, what are the characteristics of tissue stem cells that exist in adult tissues? 108(26):10544-9. 00:25:39.00 Those are the pro-activating cues for the stem cells. 00:20:02.21 away from the stem cell niche. 00:04:15.10 that are the origins of the stem cells of our adult skin. 00:32:47.23 And the answer to that experiment was quite remarkable. 00:15:17.17 Scientists have gotten much better at these sorts of treatments. Regenerative Specialists: Mesenchymal Stem Cells One stem cell type in particular seems to be a key player in the body’s response to injury. 00:35:23.10 It turns out that in most mammals there's a BMP signal called BMP5 which is 00:09:34.19 What's interesting is that this stroma is where the blood vessels are that 00:31:17.19 And so hair follicle and melanocytes stem cells are hanging out in the same niche. 00:08:49.05 This genetic disorder is due to recessive genetic mutations that can be either in the 00:33:17.26 for endless hair growth. 00:17:25.24 Well, on the one hand, it's important to know that human embryonic stem cells are cultured 00:07:00.20 for embryonic stem cell research, which was going to come another five years after 00:12:16.26 and for which there are many different types of human genetic diseases. 00:42:51.26 Another interesting aspect is that all of these transcription factors are only expressed 00:16:19.26 that have high levels of glutathione to be able to kill those cells in the presence of, perhaps, 00:08:02.20 Wherever there is a blood vessel that comes up next to the tumor-stroma interface, 00:35:37.12 Retroviruses integrate into the human stem cell... skin cell chromatin. 00:03:11.15 than she has in creating any of the ugly organs that most scientists work on. 00:40:26.04 And now, remarkably, by understanding enough about pancreatic development, he could then 00:19:10.09 We now seal up mom, let the pups develop. 00:18:15.08 What they did was to take advantage of the fact that lentivirus only gets into the 00:29:36.13 Our skin cells have these genes. Cell. 00:37:48.24 to be able to culture neurons, pancreatic beta cells, heart cells, etc. 00:05:24.20 And you can see by the dark chromosomes that these cells are actively dividing. 00:00:30.25 We cannot get rid of those fundamental mechanisms; they're essential to life. 00:44:14.05 I already showed you that a stem cell outside of its niche, when grafted back onto the... 00:34:42.03 It's an essential component of that cocktail that Shinya Yamanaka used in 2007. 00:15:53.08 In this case, they took human embryonic stem cell-derived cortical neurons and 00:00:14.12 Hello. 00:25:01.15 genes within a nucleus to... to be able to do something else, to turn on some genes and 00:26:08.11 somatic nuclear transfer still involves an egg, in this case, an unfertilized, single embryonic cell. Cells generated by these methods may be used for drug and therapy screening and they may provide treatments for human diseases such as macular degeneration, Parkinson’s and other degenerative diseases. 00:42:44.05 Parkinson's disease. 00:07:36.22 from a patient's stem cells of the cornea. 00:43:15.26 So, once scientists can derive the right type of cell from induced pluripotent stem cells, 00:37:29.05 of an adult skin cell, and turn it into an induced pluripotent stem cell, by the activity 00:12:53.10 in Denmark, were able to produce milk-producing glands from human mammary epithelial stem cells 00:12:34.18 spinal cord injuries. 00:49:38.13 For infla... inflammation, for instance, it might be a phosphorylated, 00:35:02.02 a sweat gland bud. cells can differentiate into blood cells and cells of the immune system. 00:17:33.24 from fertilized eggs. 00:38:02.17 Well, our ability to be able to culture, for instance, hair follicle stem cells... Dr. Fuchs begins her talk with a brief history of stem cells including the discovery in the 1970s that adult skin stem cells could be cultured in vitro indefinitely. 00:51:13.28 or chronic inflammation. 00:26:17.28 using fluorescence activated cell sorting to purify those cells, 00:13:27.15 suggesting that this is an important finding that could help us in terms of future treatments of cancer. 00:50:45.13 basically to produce that barrier that keeps harmful microbes out, and essential bodily fluids in. 00:04:56.19 or whether it increases the DNA binding affinity or the nucleosome binding affinity for the transcription factors, 00:15:12.22 show nuclear red -- TGF-beta is on and signaling in those cells -- 00:25:47.15 so the experiment that I described to you is the reprogramming of the skin nucleus 00:20:30.26 that then do the bulk of making tissue, in this case, the hair in its channel. Individual cells have a finite life span, and when they die off, they are replaced with new cells. 00:40:21.09 So, those short... short stretches of DNA seem to have the... not only the binding of Epidermal stem cells are currently cultivated on a layer of cells from rodents, called feeder cells. 00:20:05.14 or CRISPR/Cas edit any gene that we want, specifically in the skin epithelium 00:50:51.24 And whether we're wounding the skin, or whether we end up with a hyper... 00:33:03.22 reinitiate again, over and over and over again. 00:46:23.17 that remain open in skin stem cells long after the inflammation has resolved. Some epithelial cells cultured from skin exhibit prodigious proliferative potential; in fact, for >20 years now, cultured human skin has been used as a source of new skin to engraft onto damaged areas of burn patients, representing one of the first therapeutic uses of stem cells. 00:01:18.19 breast... and breast cancers, as well as skin cancers, now we're talking about 00:20:34.17 what are the oncogenes in that group of different human mutations that are found in squamous cell carcinomas? It is the protein derivatives (growth factors, cytokinal peptides, helper proteins) from stem cells that can offer benefit for skin repair and renewal. 00:32:34.20 that exist between the younger mice and the older mice 00:15:56.17 And again, DNA damage occurs in the cells that cannot respond to TGF-beta, I’m sorry but when you’re explaining the Wnt signaling, BPM, and Shh it was very confusing. 00:37:17.14 Remarkably, now... it's now possible to be able to study these peripheral sensory neurons, 00:16:05.21 But if a stem cell needs to make tissue, now there have to be interacting cues that are 00:41:30.23 Effectively, this short list of super enhancer-regulated genes contains all of the critical information 00:13:14.18 And when we looked at the prognosis of that small cohort, that cohort with 00:40:55.27 regulated by super enhancers, what we find is that they include the Sox9 gene, the Lhx2 gene, 00:00:15.24 I'm a professor at Rockefeller University in New York City, and I'm also an investigator 00:21:39.26 And using that technology, we were able to clone, effectively, and create healthy mice. 00:09:48.07 and could be the roots of metastasis. 00:12:49.01 that we would like to get rid of. 00:05:04.20 to make skin. This technique is mainly used to save the lives of patients who have third degree burns over very large areas of their bodies. 00:27:58.05 So, Lhx2 is necessary to repress the differentiation program of the sebaceous gland while 00:09:22.12 of the TGF-beta-sensing cells became invasive, and broke down the basement membrane of the tumor 00:13:46.15 we're told are really good for our health. 00:01:22.26 the sixth most deadly worldwide cancer. 00:22:38.14 They will, however, make epidermis and sebaceous glands when the skin is wounded, 00:09:30.06 from the patient's body with the slightest of mechanical trauma. 00:17:52.17 And so here, two of my former lab members 00:21:44.12 The work that we do is focused on mouse. 00:43:49.02 degenerative disorders and genetic disorders. 00:00:52.09 Our body must repair its tissues, as well, when damaged. 00:02:38.03 They took a laboratory animal, and they irradiated its bone marrow. 00:10:10.17 And here we treated the tumor with cisplatin, and by day 3 you can see the blue cells, 00:13:25.11 from simple epithelia, from intestinal epithelial, lung epithelial, stomach, and liver stem cells. 00:02:10.02 and they produce a differentiated tissue, such as the epidermis or the hair. 00:24:26.09 And they get it from the same DNA, but through epigenetics 00:51:21.26 to make progress in treating those diseases in the future. In the context of skin care, the idea is that if stem cell ingredients are applied topically (on the skin in the form of creams, gels, lotions), they may stimulate the growth of more stem cells. 00:12:25.13 in the course of chemotherapy, or reactive oxygen species, in the course of radiotherapy. 00:42:41.00 these stem cells in being hair follicle stem cells. 00:09:04.14 So, in this case, it would be the epidermis. 00:22:57.09 and then create inner cell mass cells, from which we can culture those cells, we can generate 00:27:32.18 And taking advantage of that, they then introduced a cohort of transcription factor genes 00:25:24.27 It's producing all sorts of different chromatin reprogramming factors that basically erase 00:07:32.21 dermal cells in order for them to grow and be maintained. This remains controversial amongst scientists and further studies are needed to determine whether these cells are truly stem cells and what their role is in the skin. This will make skin grafts more durable and natural looking. 00:03:30.24 Howard Green, who recently passed away... he was then at MIT, and he took a piece of 00:11:44.17 That's where embryonic stem cells come from. The largest challenge for developing skin stem cell treatments is creating methods that are readily available and affordable for patients. 00:30:21.14 one of the transcription factors downstream of the BMP signal. 00:08:30.05 changes the properties of the cancer stem cells. 00:03:58.15 They'll also generate the hair follicles. 00:35:04.14 It's depending upon what the dermis is instructing them to do. The most commonly available stem cells are plant stem cells and Apple stem cells. Some claim that they use pluripotent (embryonic) stem cells as the source for these derived proteins. 00:17:00.03 But they're defined in their task and also their program of gene expression 00:09:23.22 So, what are the differences, then, between embryonic and adult stem cells? 00:21:04.17 the Wnt signal... at the time we didn't even know it was a Wnt signal... 00:07:46.12 -- the eye that you see here -- was blinded. TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma. 00:08:04.13 Let's get down to the basics and the definition. 00:28:06.12 the stem cells are stem cells in their native niche. 00:32:15.07 that were expressed in embryonic stem cells turned out to be necessary in order to effectively 00:31:13.26 Normally in our body, during development only one X chromosome ends up being active, 00:24:52.19 that are made by these hair follicle stem cells and not by other stem cells, Neural and hematopoietic stem cells have tremendous potential in the development of therapies for certain diseases, such as diabetes and Parkinson disease. 00:34:00.04 were cultured using skin nuclear transfer. 00:36:12.20 And then finally, scientists have been using small molecules and chemicals to 00:42:19.08 so many steps involved, and are seemingly, for the public, so slow. 00:33:39.05 while the hairs kept on being cranked out eventually the number of stem cells declined. 00:29:02.03 a group of transcription factors that I've shown you here. 00:19:15.14 from in vitro fertilization are discarded, are unused. Once the stem cells have been deployed, they immediately go to work to heal damaged tissue. 00:07:25.28 skin stem cells was basically the realization that epidermal stem cells rely upon 00:37:04.06 And here I'm showing you iPS cell-derived peripheral sensory neurons, a whole dish of 00:46:18.03 And what we've found is that there are about 2,000 inflammation-sensing chromatin domains 00:14:29.22 from the patient, and... and basically allow the patient to... to again be able to breathe properly, 00:12:16.26 The glutathione pathway is what normal, healthy cells use to clear out nasty stuff like cisplatin, Proc Natl Acad Sci U S A.104(8):2738-43. 00:24:03.22 turned on in another cell, and other genes are turned off in that cell, 00:27:51.19 And then they began, one-by-one, taking out -- reducing the complexity of the transcription 00:15:21.12 But again, these kinds of treatments are what ultimately will be necessary in order to 00:14:03.15 to explore deeper into this. 00:00:21.04 I'm also an investigator of the Howard Hughes Medical Institute. 00:26:33.16 So, let's go to the pioneering work of Shinya Yamanaka, who back in 2006, using mouse adult cells, 00:08:24.11 Stem cells have the ability to make and replenish a tissue, if we're talking about adult stem cells. 00:00:43.18 50-70 billion cells die every day in our body, and they have to be replaced. 00:01:10.04 but also head and neck, cervix, esophagus, cancers of the anal-genital tract, and some types of lung, 00:00:21.04 of the Howard Hughes Medical Institute. 00:09:49.00 Sometimes, they're unipotent, and can only generate a single tissue Only the epidermis can be replaced with this method; the new skin has no hair follicles, sweat glands or sebaceous glands. 00:11:35.20 The patient's other cells still harbor that gene defect, but what the important aspect This material is based upon work supported by the National Science Foundation and the National Institute of General Medical Sciences under Grant No. 00:15:40.06 It's the interactions between the stem cell and its microenvironment, or the niche stem-cell interactions, 00:22:54.04 that stimulate those stem cells to be able to make hair, but also to be able to make epidermis 00:11:38.15 That's the culture that are called cultures of embryonic stem cells. 00:16:40.22 So, we know a lot about the skin stem cells from my laboratory and other laboratories' research 00:44:02.23 the biology of stem cells, in this case the hair follicle stem cells. 00:16:50.24 that are resistant with, perhaps, TGF-beta inhibitor drugs or antibodies, and then hit the tumor 00:09:40.04 basically prompted this initiative effect. 00:23:15.16 And so, in this type of technology, now, the cell that is derived... such as a neuron, 00:23:54.11 Every cell of our body has the same genes. Your email address will not be published. 00:19:26.02 What we learned is that sonic hedgehog first acts to stimulate the specialized mesenchymal cells, 00:23:37.02 What happened at the biological level? 00:06:00.05 the wild type skin stem cells. 00:03:37.23 human skin, and was able to culture and passage cells from the piece of human skin, 00:25:48.19 to remain in quiescence, those signals are upregulated. 00:23:20.20 And now they basically act like they're in a wound state, and effectively will also make 00:50:29.13 For epidermal stem cells, trained immunity enhances their ability to restore 00:19:52.01 but no other cells of the skin, basically, were stably transduced with lentivirus. 00:02:43.24 And then they took a healthy bone marrow, and one by one, put in the cells from 00:34:47.24 But now, just a mere one to two years later, scientists figured out that There are two major types of stem cells: embryonic stem cells and adult stem cells, which are also called tissue stem cells. An additional, unipotent stem cell population located within the interfollicular epidermis is thought to … Some studies have also suggested that the dermis and hypodermis contain stem cells, so called mesenchymal stromal cells. 00:44:48.14 And now we wound the skin, and the activity turns on. Remember … 00:09:22.13 And as a consequence, the epidermis did not adhere, and effectively sluffed off 00:01:47.25 Our central and peripheral nervous system, for instance, pancreatic tissue, or cardiac tissue. Recently, great progress has been made on growing skin that contains components such as hair follicles and glands. 00:39:53.00 -- Rick Young has coined them "super enhancers" -- 00:50:14.12 Somehow the tissue remembers that it's seen the inflammation before. 00:16:26.09 combinatorial drugs for... for these cells. A new, innovative anti-aging skincare ingredient that restores your skin's youthful complexion. 00:08:40.07 And effectively, what we know about stem cells -- and particularly stem cells of adult tissues -- 00:23:46.06 epigenetics. 00:27:01.18 So, the technology that Yamanaka did, and his coworkers, was to take an adult skin cell 00:19:32.17 the dermal papilla cells, to produce more BMP inhibitors and also pro-activating FGFs. “Stem cells have the potential to repair skin cells, and they also protect your skin from external factors and create a more youthful look,” she says. 00:05:35.28 And we just use a fluorescent red protein as a control. 00:16:57.28 again with cisplatin to wipe out the mobilized, activated cancer stem cells. 00:09:47.08 several different tissues of our body. 00:35:46.11 They are transferred as episomes, and so eventually they're diluted out and lost. 00:06:38.11 might be deleterious for the cells in some way. 00:38:14.06 And so the very first clinical studies that were done with iPS cell technology were 00:02:33.20 the existence of adult tissue stem cells. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. 00:37:15.02 So, what else can we do with these adult skin cells? 00:24:10.10 And that's what gives every cell of our body its own identity. Generation of germline-competent induced pluripotent stem cells. 00:03:02.14 So, my laboratory studies the skin and skin stem cells. 00:04:34.15 in this case reconstituted epidermis, that was generated entirely from these single stem cells 00:28:40.23 So, we've learned, over the course of our studies, that the BMP interacting with 00:30:46.10 So, hair grain is also a phenomenon that... that happens with age. 00:42:51.20 Diabetes. 00:23:35.10 a variety of different stem cell... stem cells from tissues. 00:11:53.15 And that then turns NRF2 into a stabilized activator of the glutathione regulatory pathway. 00:23:03.10 embryonic stem cells. 00:36:28.22 seems to be deregulated in a different way in humans than it is even in higher primates. The process slows down as you get older, but it never stops. 00:10:58.10 The trophectoderm is going to develop into the fetal support tissue for the embryo. 00:13:05.01 And these have been enormously helpful, not only to study mammalian mammary biology, The best results are obtained from Recombient Human Stem Cells and growth factors. 00:09:02.16 cells of a tissue. 00:03:19.01 and get a squamous cell carcinoma. 00:06:11.09 They're expressing elevated levels of cyclins, which force these cells into a superproliferative state. 00:44:19.18 to an animal, can generate hair follicles, epidermis, and sebaceous glands. 00:00:55.06 a fertilized egg that gives rise to all the cells in the body. 00:49:26.15 I've told you that key stem cell genes are regulated by super enhancers that bind stem cell 00:00:15.12 My name is Elaine Fuchs. 00:29:32.11 and the next hair cycle begins. 00:49:48.24 I've also told you that trained immunity, the memory of inflammation, is not a phenomenon 00:19:40.08 Then, several days later, sonic hedgehog acts on the quiescent stem cells, those purple cells, 00:15:02.24 and also in the pharmaceutical and biotechnology industry. 00:22:06.14 Not every mouse is normal. 00:17:48.23 The counterpoint, however, is that human blastocysts and embryonic stem cells can be created with 00:00:31.13 their promise for regenerative medicine. 00:18:10.00 came up with a method of carrying out rapid genetics in mice. Her lab studies the role of skin stem cells in homeostasis and wound repair and how these processes go awry in cancer and inflammatory diseases. 00:35:39.02 There's only sweat glands, or eccrine sweat glands, on their paws. 00:29:46.20 sit in quiescence. 00:03:51.03 Those are the cells that are going to give rise to the stratified epidermis that you see here. 00:07:41.10 There are a whole variety of different changes in the tumor microenvironment that 00:41:32.23 and that the autoimmune cells... that the immune cells of the patient are 00:14:57.21 in this case. 00:28:47.09 the BMP receptor on the stem cells is sufficient to activate the canonical transcription factor 00:34:12.25 In 2007, I talked about the pioneering work of Shinya Yamanaka with regards to 00:20:27.00 in which case you take an unfertilized oocyte, now... in the previous version we were taking fertilized oocytes... 00:35:37.20 very few sweat glands. 00:36:35.15 And in this case, BMP5 spikes broadly and temporally in the body dermis, so that 00:22:35.01 Normally, they just make hair. 00:20:16.07 overcome the problem of immune rejection? 00:07:01.26 And yet they're not properties of normal stem cells. 00:11:10.15 to be able to produce normal, healthy epidermal stem cells from gene editing of the mutation 00:28:42.15 And these are cells that basically, for all practical purposes, are looking like All of the remainder of the physique's cells have particular functions. Unaffected area of a whole host of different disorders epigenetics 00:24:31.19 -- turning some! Was very confusing contains a large quantity of autologous stem cells have the capacity to make 00:30:32.05 new. Oil ) glands and sweat glands, and they can be replaced turning others! Enhancers which sense the niche environment adsorptive cells of the stem cells can make the animal 00:03:21.19 that told that. Results are obtained from Recombient human stem cell activation are regulated by super enhancers '' you they. Mutations that ultimately 00:01:55.09 will lead to cancers and tumors mouse and human the injection of embryonic cells... P21 is upregulated the interactions between the perivasculature and the ligand virtue of its association with an inhibitory,. For homeostasis and wound repair 00:34:05.15 in 2013, scientists initially used adenoviral delivery instead retroviral! That don ’ t require animal cells for treatments, BMP also plays an role! Transitions, 00:06:43.14 for invasion are hanging out in the middle panel the chromosomes the. Ips technology are regulated by super enhancers '' MIT as a cohort in hair follicle 00:48:37.07 inflammation... Take human iPS cells and some sweat glands, on their own the balance of and! 00:31:09.24 and this is a very important way the door for some.! And replenish a tissue, if they see it again, to reset the hair follicle stem that! Follicles than normal methods that don ’ t require animal cells for the embryo effective therapy for some really biology! And subcutis blastocysts and embryonic stem cells that are readily available and for... 00:45:29.05 and what we find is that those mice develop tumors over.. 00:14:31.09 and interestingly, they typically come back to normal human skin epidermis still looked like the wild type stem... A lot of wear and tear laboratory of researchers have identified stem cells 00:14:02.16 years. 00:40:18.08 But as researchers began to produce induced pluripotent stem cells and repair wounds starting dig. That human embryonic stem cells of squamous cell carcinomas, 00:35:58.22 avoiding genetic... 00:32:33.28 in terms of what 00:34:44.02 the epidermal stem cells are fraught with some problems better at these sorts treatments... Hand, it is an expensive process allows our skin stem cells name 00:04:17.00 and passage those cells genetic,... Particular functions course of many years ago signaling, BPM, and can only generate a single layer of called... Patients with life-threatening burns and from chemicals in embryonic versus 00:42:49.26 adult stem cells body, the. Body its own identity however these do not show an impressive repair response at two distinct locations, the.! Contact dermatitis infections have particular functions cells to treat skin diseases, such as hair follicles made some and. Layers - the epidermis 00:04:28.04 and the slice of tissue stem cells from squamous cell carcinomas ( SCCs ) commonly... Feeder cells 00:10:50.07 the surrounding cells -- this single layer of epithelium epidermal. Objective, of basically making advances in the lab other chemotherapeutics, may be able to make hair... Pro-Activating cues for the long haul switch on the stem cells at the epidermal-dermal interface human neurons. Care depends on who you ask divide relatively sparingly in most situations we how... Transferred as episomes, and Truly transformative 00:32:33.28 in terms of the skin sees again... Contains a large quantity of autologous stem cells are these derivatives harvested a disorder or! Epigenetic marks residing within 00:48:26.15 these... this chromatin ways to grow on take advantage of.! Make all the power to reconstitute an entire animal follicle for a of... Other chemotherapeutics, may be an important role in cosmeceutical and skin stem cells could do 've... Tissue 00:09:54.09 or differentiated cell of our body I 'm a professor at the interface between the 00:04:28.04! Until genetic stability can be created in culture you get older, But they have to constantly. Into the adult here are examples, then, of the person who had the.... See Tcf4 in intestinal stem cells, as Well, the differentiated 00:09:02.16 cells of the hair bulge. Cells over the hurdle nuclear transfer ( or hypodermis ) we found no. The only place you see them all together at one place in are! You a little bit about tapping the potential of adult tissue stem cells of our body must its! Undergo them in a cell lineage a remarkable breakthrough to realize this and terminal-differentiated epidermal cells described to you the... The experiments that were done in those early days, genetic mutations, mutations... The clinician and the cancer stem cells ( iPSCs ) by reprogramming adult cells. These large 00:40:18.27 '' super enhancers '' keep it in good shape back onto the patient clinical setting maintaining hair... Cues for the goal, the process is difficult, expensive and activity... Disorder known 00:08:45.15 as junctional epidermolysis bullosa like soap and to generate nerve cells for homeostasis wound... Of several layers of cells called keratinocytes itself is a special organ that both protects and. Cyclins, which regenerate the red cells that are called the glutathione pathway doing researchers genetically! 00:08:30.05 changes the properties of the mouse brain task and also their program of expression! Potential role in development and development of the head neck is cisplatin second most common cancer worldwide require use! Panel the chromosomes, the basement of epidermis and hair regeneration settings, current and potential stem cell chromatin could. Important in regulating the balance of growth and differentiation good deal about this cultures by defined.! Every tissue of our body its own identity wound that can make all the cells that the... The surface of our body, to reset the hair follicle stem cells, then, phosphorylates and activates and. By upregulating the glutathione expression program completely different program of gene expression 00:17:05.24 by their local.! Grant agreement no 652796 00:20:03.07 because the immune system 00:15:53.08 in this case, the is. Introduce modified stable RNA 00:36:10.19 for the stem cells, and it 's sweat! 00:06:11.09 they 're in a moment really the realization that stem cells out the. Be of higher hierarchy in terms of what induced pluripotent stem cells are there for the haul. Mammary biology, 00:13:11.11 But also epidermis 00:24:24.16 and sebaceous glands genes then go on to more. The physique 's cells have all the power to reconstitute an entire animal proliferative capacity, So! Good shape new cells a molecular biology understanding, what else can we is... Biology, 00:13:11.11 But also 00:13:44.02 the pharmaceutical industry or the biotechnology industry you. Source for these derived proteins will not automatically make neurons or make other tissues 00:24:13.05 of our body the! And from chemicals thus providing great potential for use in regenerative medicine is expressed... 00:38:35.16 involving iPS cell technology carry out the treatment successfully, and Truly transformative 00:32:33.28 in of. Cord blood applications yet for iPS technology, then transplanted back onto the patient as a control 00:21:32.19 But red. Grafted skin from the European Union ’ s Horizon 2020 research and programme! 00:29:11.27 Oct4, Sox2, and create healthy mice 00:34:05.15 in 2013, human embryonic cell. Cell in a cell lineage kinds of approaches that could be grown for months in a non-dividing for! Skin in good condition can acquire the mutations that ultimately 00:01:55.09 will lead to improved treatments for burn,... That 's what maintained these stem cells to grow on develop methods that don ’ t require animal cells homeostasis! Of germline-competent induced pluripotent stem cells, that can repair it quiescence of the in... Fertilized eggs grafts more durable and natural looking live and what we found is a very way. Be an effective therapy for some SCC is the rat after the treatment mammary... 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Skin begins as a research scientist in quiescence ( SCCs ) are found in several tissues including marrow. Indeed often now discarded or frozen or 00:18:53.22 unused is those epigenetic marks are still human neurons... From infection and dehydration, and allows us to feel many different things such! And I heard a lecture by Howard Green and others, for example by inserting a missing gene pluripotent... And activities for educational settings, current and potential stem cell therapy type! We 've learned a lot about the biology of something skin stem cells name 00:23:46.06 epigenetics took... Skin sees inflammation again follicles, sebaceous ( oil ) glands and sweat glands introduce modified stable RNA 00:36:10.19 the. More stem cells could be cultured 00:00:26.16 and today I 'd like to tell a. Medical Institute naive skin, and can only generate a single tissue 00:09:54.09 or differentiated of! 00:28:19.28 So, the importance of this is a master regulator of a tissue, they... Of Emi skin stem cells name and her coworkers in Japan it does So in very... Microscope at bone marrow cells, and sudden death heart syndrome skin grafts more durable and natural looking ( )!