GSE135144 NFI Transcription Factors Govern Stem Cell Chromatin Accessibility and Guard Against Irreversible Hair Loss ATAC-seq

Contributors : Hanseul Yang ; Rene Adam ; Elaine FuchsSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusTissue homeostasis and regeneration rely upon resident stem cells (SCs), whose behavior is regulated through niche-dependent crosstalk. The mechanisms underlying SC maintenance are still unfolding. Here, using hair follicles (HFs) as model and spatiotemporal gene ablation in mice, we uncover transcription factors (TFs) NFIB and NFIX as guardians of the process. Complete NFI ablation causes SC depletion and hair loss which resembles irreversible alopecia in humans, who intriguingly also display reduced NFI. Through single cell transcriptomics, ATAC- and ChIP-seq profiling, we uncover a key role for NFIB/NFIX in governing chromatin accessibility of HFSC master TFs . When NFIB/NFIX are genetically removed, the stemness epigenetic landscape is lost, as enhancers driving HFSC identity are decommissioned and those of epidermal differentiation and wound-repair are de-repressed. Together, our findings expose NFIB/NFIX as crucial rheostats of tissue homeostasis, functioning to safeguard the SC epigenome from a breach in lineage confinement that otherwise triggers irreversible tissue degeneration.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Contributors : Hanseul Yang ; Rene Adam ; Elaine FuchsSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusTissue homeostasis and regeneration rely upon resident stem cells (SCs), whose behavior is regulated through niche-dependent crosstalk. The mechanisms underlying SC maintenance are still unfolding. Here, using hair follicles (HFs) as model and spatiotemporal gene ablation in mice, we uncover transcription factors (TFs) NFIB and NFIX as guardians of the process. Complete NFI ablation causes SC depletion and hair loss which resembles irreversible alopecia in humans, who in...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
Contributors : Hanseul Yang ; Rene Adam ; Elaine FuchsSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusTissue homeostasis and regeneration rely upon resident stem cells (SCs), whose behavior is regulated through niche-dependent crosstalk. The mechanisms underlying SC maintenance are still unfolding. Here, using hair follicles (HFs) as model and spatiotemporal gene ablation in mice, we uncover transcription factors (TFs) NFIB and NFIX as guardians of the process. Complete NFI ablation causes SC depletion and hair loss which resembles irreversible alopecia in humans, who intriguingly als...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Contributors : Hanseul Yang ; Rene Adam ; Elaine FuchsSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusTissue homeostasis and regeneration rely upon resident stem cells (SCs), whose behavior is regulated through niche-dependent crosstalk. The mechanisms underlying SC maintenance are still unfolding. Here, using hair follicles (HFs) as model and spatiotemporal gene ablation in mice, we uncover transcription factors (TFs) NFIB and NFIX as guardians of the process. Complete NFI ablation causes SC depletion and hair loss which resembles irreversible alopecia in humans, who intriguingly als...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
In this study, we investigated the link between AF and senescence markers through the assessment of protein expression in the tissue lysates of human appendages from patients in AF, including paroxysmal (PAF) or permanent AF (PmAF), and in sinus rhythm (SR). The major findings of the study indicated that the progression of AF is strongly related to the human atrial senescence burden as determined by p53 and p16 expression. The stepwise increase of senescence (p53, p16), prothrombotic (TF), and proremodeling (MMP-9) markers observed in the right atrial appendages of patients in SR, PAF, and PmAF points toward multiple inter...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In this study, we hypothesized that moderately and chronically reducing ACh could attenuate the deleterious effects of aging on NMJs and skeletal muscles. To test this hypothesis, we analyzed NMJs and muscle fibers from heterozygous transgenic mice with reduced expression of the vesicular ACh transporter (VAChT), VKDHet mice, which present with approximately 30% less synaptic ACh compared to control mice. Because ACh is constitutively decreased in VKDHet, we first analyzed developing NMJs and muscle fibers. We found no obvious morphological or molecular differences between NMJs and muscle fibers of VKDHet and contro...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, a polypharmacology approach of combining established, prolongevity drug inhibitors of specific nodes may be the most effective way to target the nutrient-sensing network to improve late-life health. Deletion of p38α in Neurons Slows Neural Stem Cell Decline and Loss of Cognitive Function in Mice https://www.fightaging.org/archives/2019/10/deletion-of-p38%ce%b1-in-neurons-slows-neural-stem-cell-decline-and-loss-of-cognitive-function-in-mice/ Researchers here provide evidence for p38α to be involved in the regulation of diminished neural stem cell activity with age. It is thought...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Xia J, Minamino S, Kuwabara K, Arai S Abstract Stem cells are an undifferentiated cell population that has the ability to develop into many different cell types and also has the ability to repair damaged tissues in some cases. For a long time, the stem cell regenerative paradigm has been based on the assumption that progenitor cells play a critical role in tissue repair by means of their plasticity and differentiation potential. However, recent works suggest that the mechanism underlying the benefits of stem cell transplantation might relate to a paracrine modulatory effect rather than the replacement of a...
Source: BioScience Trends - Category: Biomedical Science Tags: Biosci Trends Source Type: research
This article, unfortunately paywalled, is interesting to note as a mark of the now increasingly energetic expansion of commercial efforts in longevity science. David Sinclair has been building a private equity company to work in many areas relevant to this present generation of commercial longevity science; while I'm not sold on his primary research interests as the basis for meaningful treatments for aging, he is diversifying considerably here, including into senolytics, the clearance of senescent cells demonstrated to produce rejuvenation in animal studies. This sort of approach to business mixes aspects of investing and...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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