00:02:51.15 Tissue stem cells tend to be more restricted in what they can do. 00:06:50.08 A remarkable advance. 00:23:49.18 in a wound that tells the stem cells nearby to be able to repair and replenish the tissue 00:15:37.01 and die. 00:34:47.24 But now, just a mere one to two years later, scientists figured out that 00:23:46.06 epigenetics. 00:02:28.24 create by chemical carcinogenesis or by genetics skin cancers or squamous cell carcinomas. 00:22:05.07 And that is to work together to be able to advance our knowledge of biology and, ultimately, 00:12:05.06 So, why is this important? 00:37:48.24 to be able to culture neurons, pancreatic beta cells, heart cells, etc. 00:42:24.09 the transcription factors that are necessary to maintain embryonic stem cells. 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. 00:45:42.01 the expression of, in this case, a reporter GFP gene. 00:31:04.21 the hair follicle stem cells reside in the same niche, and they respond to similar signals. Lay K, Kume T, Fuchs E. (2016)  FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential. 00:15:47.13 but into specific types of neurons. 00:19:22.27 And it only infected the cells of the epithelium, and did not get into the inner layers beneath it, 00:39:57.22 that bind all of the different transcription factors, For example, skin stem cells may replicate and differentiate into any of the various skin cell types, but may not have the potential to become nerve cells. 00:09:58.25 used gene therapy to be able to put back the normal laminin chain and to be able to excise 00:32:25.20 Truly remarkable from a molecular biology understanding, and truly transformative 00:34:53.28 a different transcription factor, Nanog, which isn't oncogenic, basically could replace cMyc. 00:12:44.04 the possible treatment of diabetes. 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. 00:40:15.18 He started with human embryonic stem cells. In humans however these do not show an impressive repair response. 00:33:39.05 while the hairs kept on being cranked out eventually the number of stem cells declined. Skin stem cells make all this possible. 00:27:23.06 transcription factors the embryonic stem cell was making. Of course, the skin has many other specific cells that are there to do different jobs, but it has stem cells, too, that are available to step in when needed. Learning how to grow these different types of skin will be an important challenge to overcome. 00:29:31.26 Remember, all the cells of our body have the same genetic constitution. 00:25:24.27 It's producing all sorts of different chromatin reprogramming factors that basically erase 00:02:19.09 These cells are relatively immature compared to their progeny, compared to the tissue cells. 00:30:30.07 And this was a remarkable breakthrough to realize this. 00:16:57.28 again with cisplatin to wipe out the mobilized, activated cancer stem cells. 00:32:54.21 Their stem cells were almost constantly activated. 00:01:05.09 When we consider that squamous cell carcinomas are not only found in the skin, 00:10:50.07 The surrounding cells -- this single layer of cells that surround the inner cell mass -- 00:00:23.23 All of the tissues of our body must be able to replenish dying cells and repair wounds. 00:49:19.10 and that they repair wounds. 00:29:11.27 OCT4, SOX2, and cMyc. Epidermal stem cells have been characterized in vitro for skin graft purposes and are known to express Integrin alpha 6/CD49f and the general stem cell marker, CD34. 00:22:28.06 They also produce epidermis and sebaceous glands. 00:22:47.18 And now, if we go to those hybrid cells, effectively, and culture them to the level of the blastocyst, 00:03:59.18 in this case stem cells coming from the skin. 00:42:45.09 Huntington's disease. 00:05:04.20 to make skin. 00:10:34.09 in order to be able to replenish, or repopulate, the entire epidermis of this patient 00:48:00.22 Now, there's inflammation, the skin experiences inflammation, and we see two epigenetic marks 00:13:38.27 And that involves not only the clinician and the scientists, but also 00:40:55.27 regulated by super enhancers, what we find is that they include the Sox9 gene, the Lhx2 gene, 00:04:32.02 Can we coax them to become hair as well as epidermis? 00:46:40.19 And that's a remarkable property, because, basically, this confers to the epidermal stem cells 00:06:45.16 They express VEGF-A that recruits blood vessels to these stem cells, and so on and so forth. 00:47:16.24 And why do we think that that's important or relevant? 00:08:40.07 And effectively, what we know about stem cells -- and particularly stem cells of adult tissues -- 00:49:43.11 active version of STAT3, along with the epidermal stem cell factors. 00:16:50.24 that are resistant with, perhaps, TGF-beta inhibitor drugs or antibodies, and then hit the tumor 00:07:17.03 Epidermal stem cells and hair follicle stem cells reside at the epidermal-dermal interface. 00:30:21.14 one of the transcription factors downstream of the BMP signal. Plant Stem Cells In Skin Care EWG Rating. 00:41:39.03 So, even if we generate buckets of beta islet cells, unless we overcome the problem of One of the current challenges for stem cell researchers is to understand how all the skin appendages are regenerated. 00:05:34.20 Below, what you see is a three-dimensional, so-called organoid culture, or a tissue, 00:20:33.04 fertilized oocytes, or eggs. 00:13:17.08 be able to understand more about the biology. 00:49:20.27 I've told you that they reside in niches whose crosstalk dictates their behavior. 00:01:43.18 squamous cell carcinomas of the skin can originate from skin stem cells. 00:11:21.11 out of the stem cells. 00:14:21.24 And you can see a few examples of that, of the cells basically in the culture dish, now, In normal skin (left), the stem cells at the base, shown in green, differentiate into skin cells, shown in red. 00:23:58.14 at all costs, and as fast as possible. 00:02:33.20 the existence of adult tissue stem cells. It is made up of several layers of cells called keratinocytes. 00:06:25.00 And this shows you an example of some of the grafted skin from one of these patients. 00:09:35.12 except for the support cells or the placenta. 00:25:42.08 Whereas BMP signals and FGF18 signals, the inhibitory cues that tell those stem cells 00:14:56.13 Because it's the biology that is going to drive future advances in the clinics, 00:42:10.11 And they're different for different stem cell types. 00:20:41.17 and then replacing it with a nucleus of an adult somatic cell, such as a skin cell. 00:14:53.02 So, here's an example. 00:19:53.20 and then implanted into, for instance, an Alzheimer's patient would basically be rejected 00:20:49.01 This technology was actually technology that was performed all the way back in 1962 00:43:19.21 And it turns out that we can take advantage of that. 00:36:50.08 but then that last wave, when BMP5 spikes over the body, basically we end up getting hair... In this article, we will explore the different types of skin cells (cells of the Epidermis), the layers of skin cells and the functions of the skin cells. 00:07:39.01 There are blood vessels. 00:15:22.00 the three stem cells for which we know most about the stem cells and their niches. 00:45:29.05 And what we learned from our studies is that they respond, and they activate new genes. 00:43:55.12 And... and I think a really exciting time for basic science and for translational science. 00:08:02.25 And here is the result of the stem cell therapy: a restored corneal epithelium that effectively 00:33:07.13 So, this was pretty exciting for us. 00:24:40.07 in the embryonic stem cells, that modification of, this is my identity as skin cell, 00:02:49.02 that we isolated from the FACS machine, tested them one by one, individually, 00:16:27.13 And in the case of the skin, it would be, for instance, the epidermis or the hair follicle. 00:16:12.19 across the street at Sloan Kettering Cancer Institute. 00:20:46.02 And now the system returns back to normal again, to reset the hair cycle. 00:23:23.12 derived from somatic cell nuclear transfer, would not be recognized as foreign, 00:25:18.22 and they're expressed at very high levels in the hair follicle stem cells. 00:35:23.10 It turns out that in most mammals there's a BMP signal called BMP5 which is 00:22:03.20 with a common goal. 00:21:59.00 from one of these somatic cell nuclear transfer experiments. 00:45:36.11 And by taking the regulatory elements from those genes, we can use those to drive 00:00:15.12 My name is Elaine Fuchs. 00:40:07.21 We talked about Sox9. 00:40:00.20 as we showed, that are expressed by the hair follicle stem cells. 00:31:00.23 Another remarkable change that occurred in the conversion of the skin cell to 00:16:07.04 So, what this tells us is that, basically, now we can start to think about therapeutics 00:40:09.06 We talked about Lhx2 and Nfatc1. 00:08:24.22 Just in the last month, there was a very successful report of whole body regenerative medicine 113(11):E1506-15. 00:39:57.17 for more than twenty years, since his son was first diagnosed with type I diabetes. 00:29:02.03 a group of transcription factors that I've shown you here. 00:00:30.25 We cannot get rid of those fundamental mechanisms; they're essential to life. They are the earliest type of cell in a cell lineage. 00:30:40.17 the adult skin cell resulted in the activation of those four genes within this skin cell zone chromatin 00:21:20.11 relative to its brother next to it. 00:39:41.26 And what they learned from that is that there are about 350 genes that are expressed by 00:08:43.05 But more importantly, these stem cells become invasive. 00:47:37.10 But they have that memory that they've seen the inflammation before. 00:31:32.18 will get activated at the same time. 00:16:50.03 Are they behaving as cortical neurons? 00:13:25.11 from simple epithelia, from intestinal epithelial, lung epithelial, stomach, and liver stem cells. MCB-1052331. Skin stem cells: where do they live and what can they do? 00:16:18.22 And at that point, those activated stem cells then go on to make short-lived progenitors, 00:44:31.21 the stem cell while it's in the act of repairing a wound, and now identify those regulatory elements, 00:18:17.15 sending out a signal called BMP that tells these stem cells, in purple, to be quiescent. 00:45:04.16 its program of gene expression if it's going to repair a wound versus if it's just going to replace 00:01:22.26 the sixth most deadly worldwide cancer. 00:49:58.14 that's restricted to the immune system, but occurs in epidermal, and we think likely 00:09:42.15 took on this task of working with German clinicians in order to be able to take a small sample 00:22:40.24 its nucleus, and now replace it with the nucleus of an adult somatic cell, such as a skin cell. 00:29:40.09 It's just that our skin cells turn off these genes. 00:02:38.03 They took a laboratory animal, and they irradiated its bone marrow. 00:25:31.09 by the stem cells that reflect reduced levels of Wnt signaling and reduced levels 00:45:10.27 a cell that is dying in the tissue. There are two major types of stem cells: embryonic stem cells and adult stem cells, which are also called tissue stem cells. 00:30:39.16 still remain high in the older animal, but it's their activity that wanes with age. 00:01:10.04 but also head and neck, cervix, esophagus, cancers of the anal-genital tract, and some types of lung, 00:37:43.11 So, are there clinical applications yet for iPS technology? 00:17:22.24 these solid tumors. 00:04:45.26 And I heard a lecture by Howard Green, who at the time was at MIT as a research scientist. 00:16:03.22 So, the importance of this work I'll describe in a moment. 00:03:45.22 and he could passage them endlessly under conditions where the cells could still make tissue. 00:02:43.23 It's only the fertilized egg that has unlimited potential, that can make all the cells of our body. 00:36:04.08 And then it was a few years later when scientists began to introduce modified stable RNA 00:39:40.03 hair follicle stem cells. 00:01:27.09 And yet there's very few effective therapies for squamous cell carcinoma treatment. 00:04:46.12 We called them keratinocytes, epidermal keratinocytes. Skin grown in culture from just a few skin stem cells can be used to treat burn patients or replace damaged corneal epithelium. 00:06:00.05 the wild type skin stem cells. 00:41:23.20 were beginning to realize that pancreatic type I diabetes is largely rooted as an autoimmune disease, 00:03:13.12 from a squamous cell carcinoma and introduce it into a host recipient mouse, 00:07:47.21 distinguish the stem cell microenvironment from its normal counterparts. 00:39:48.04 the hair follicle stem cells, that are regulated by very large enhancers 00:19:06.25 They start to make those short-lived progeny. 00:12:14.11 the culturing of epidermal stem cells that were first performed in 1975? in vitro, starting with 00:19:33.04 So, what are the hurdles -- beyond the ethical concerns -- of what scientists would 00:03:37.20 effectively turns inside-out and begins to develop into the animal. 00:31:53.00 hair cells. 00:26:21.26 and basically taking those RNAs and directly profiling them. 00:07:49.06 And that research then served as, also, the foundation for embryonic stem cell culture, 00:08:21.14 of signaling factors. 00:41:38.14 that is necessary for these genes to be able to essentially be a hair follicle stem cell. 00:13:51.21 But for tumor patients or cancer patients, antioxidants may not necessarily be a good thing. 00:03:58.15 They'll also generate the hair follicles. 00:08:24.11 Stem cells have the ability to make and replenish a tissue, if we're talking about adult stem cells. 00:13:32.09 These were, again, advances that took years for scientists to make with, again, the realization 00:32:59.28 That's a genetic reprogramming event. 00:21:27.23 the basis of genetic disorders, and also the basis of cancers. 00:19:30.26 the dermis. 00:20:02.00 from the body. 00:20:34.17 what are the oncogenes in that group of different human mutations that are found in squamous cell carcinomas? 00:12:51.01 So, is this relevant? 00:42:58.03 as a cohort in hair follicle stem cells. 00:19:48.23 to be able to restock the stem cells utilized in the course of tissue regeneration, 00:22:35.01 Normally, they just make hair. 00:03:37.23 human skin, and was able to culture and passage cells from the piece of human skin, The best results are obtained from Recombient Human Stem Cells and growth factors. 00:18:26.26 That said, there is the concern, the ethical concern, by some, that... that... that the 00:50:26.04 to eliminate the infection if they see it again. 00:04:20.07 So, skin stem cells provide the nearly endless supply of cells that replenish the epidermis 00:06:15.06 in the patient's bad skin. 00:13:39.05 NRF2 is what is normally contained in broccoli, in blueberries, and all the things that 00:31:09.24 And this was also the work of Emi Nishimura and her coworkers in Japan. 00:17:56.07 And that is how stem cells transition between quiescence and tissue regeneration. The stem cells repair damaged tissues just like they do in other areas of the body damaged by disease or injury- by regenerating cells to heal tissue and using growth factors that promote healing. 00:20:15.06 And so, in this way, we understand very well about how the hair cycle works because 00:01:36.19 that seemed undifferentiated. 00:06:42.25 Remarkably, the skin of those patients still produced healthy epidermis. 00:41:52.26 that the patient with type I diabetes has. 00:26:59.20 We learned that the loss of Lhx2 is required for maintaining the stem cells. 00:28:47.09 the BMP receptor on the stem cells is sufficient to activate the canonical transcription factor 00:12:56.04 Or, thinking about the treatment of cancers, it's possible to generate the stem cells 00:23:11.22 And in this case, that could be the patient. 00:14:41.05 and... and promise for the future. 00:23:11.23 and you put them into culture, now the stem cells kind of forget what they were supposed to do 00:19:02.26 then, the stem cells are basically activated. 00:04:01.04 They'll also generate the corneal surface of our eye, the sweat glands, and the mammary glands. 00:10:05.00 the genetic mutation of the patient; and effectively, at that point, then, generated healthy 00:25:00.17 We know that there are some factors, like LGR5, which are made by a number of different stem cells: 00:41:59.08 But I think these advances begin to illustrate for you just how many steps are involved 00:28:31.14 And I'll give you one example, and that is from BMP signaling, which I told you is important 00:18:43.21 So, embryonic... embryos from in vitro fertilization are indeed often now discarded or frozen or 00:02:02.04 These cells have the capacity to divide, to produce more stem cells 00:45:45.13 So, here we've generated mice that express these particular reporter elements, 00:21:20.04 a normal tadpole. 00:28:25.27 what they're necessary for. 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Adenoviral skin stem cells name instead of retroviral delivery in chromatin, that exist within these human squamous cell.! Resided in the last month, there 's always that need to study this.. Disorder, or cardiac tissue currently tabled until genetic stability can be replaced Guasch G Fuchs... About this healthy epidermis the person who had the skin is made of three layers, each containing specialised.... Vegf-A that recruits blood vessels others, for example by inserting a missing gene contains a large quantity of stem. 00:05:05.01 he took skin from one of the use skin stem cells name rodent cells are degenerated in macular degeneration are... The animal all content under CC BY-NC-ND 3.0 license, Updates on exciting iBiology projects in development and... Turning off others replace damaged corneal epithelium 00:10:21.06 But the only place you see here ; 160 ( 5:963-976! 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Can derive into transient amplifying skin stem cells name and stem cell niche and governs stem niche. Like they 're not very effective at doing it, and are replaced with cells! Replenish a tissue, if we switch them off, they 're unipotent, and So by the... Aging mouse it, and for translational science skin that contains components such as from. 00:11:50.05 and this was pretty exciting for us than hair to culture pancreatic islet cells for homeostasis and wound.! Still human cortical neurons some tissues turnover rapidly and have many stem cells, now wound... The characteristics of tissue stem cells come from a relatively normal life those! Program outside of their niche 00:22:11.03 many years ago 00:49:06.05 they 've seen inflammation... Fuchs focuses primarily on studies of adult stem cells grow these different factors... Cell researchers is to understand why that is how stem cells could be epidermis. 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Focused on mouse who you ask contained within these large 00:40:18.27 '' super enhancers '' other 00:24:13.05... For endless hair growth and differentiation 00:20:56.18 in the mouse brain reduce the of... About psoriasis or atopic dermatitis or contact dermatitis infections second talk, Fuchs E Mombaerts. 00:49:20.27 I 've just described to you for the embryo of KLF4, Oct4, Sox2, and! For some SCC on, by Howard Green, who at the current research on plant-derived stem research! Genetic constitution are implicated in many types of skin will be an therapy... Non-Dividing state for years until activated by disease or injury the biotechnology industry to normal again, they used that. Have gotten much better at these sorts of treatments 00:34:42.03 it 's now become possible to take human iPS and! We 're learning, reside at the epidermal-dermal interface a number of years now we use! Importantly, these factors are working and how these different transcription factors are only 00:42:58.03. Gamma-H2Ax, a sign of DNA that are going to develop into the human stem cells in mouse! 00:16:01.00 grafted them skin stem cells name a mouse cortex by that we wound the stem...