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Single cell analysis of transcriptome and open chromatin reveals the dynamics of hair follicle stem cell aging [scRNA-Seq]

ABSTRACT: As the biggest organ of human body, skin and its appendages offer excellent experimental systems for aging studies. Skin wrinkling, hair greying and hair loss are among the most striking and observable traits of aging. However, the chronic changes and cell-to-cell variation accumulated during aging in different hair follicle lineages remain unexplored. Here we present a detailed analysis of scRNAseq and scATACseq data from young and aging animals. We found distinct cellular state changes of individual hair follicle populations.

ORGANISM(S): Mus musculus

PROVIDER: GSE227782 | GEO | 2023/06/25

REPOSITORIES: GEO

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Single cell analysis of transcriptome and open chromatin reveals the dynamics of hair follicle stem cell aging [scATAC-Seq]

Project description:As the biggest organ of human body, skin and its appendages offer excellent experimental systems for aging studies. Skin wrinkling, hair greying and hair loss are among the most striking and observable traits of aging. However, the chronic changes and cell-to-cell variation accumulated during aging in different hair follicle lineages remain unexplored. Here we present a detailed analysis of scRNAseq and scATACseq data from young and aging animals. We found distinct cellular state changes of individual hair follicle populations.

2023-06-25 | GSE227783 | GEO

Single Cell and Open Chromatin Analysis Reveals Molecular Origin of Epidermal Cells of the Skin

Project description:Skin and its appendages such as hair follicle and sweat gland are formed by Keratin-5 expressing (Krt5+) epidermal cells that are specified from primitive, Keratin-8 expressing (Krt8+) ectodermal progenitors shortly after gastrulation. Here we show that transcription factor ∆Np63 is required for converting Krt8+ ectodermal progenitors to Krt5+ epidermal progenitors and priming the underlying dermal cells to form dermal condensate by activating the Wnt/ß-Catenin pathway. These findings unearth the molecular cascades during the fate specification of epidermal cells, illuminate the essential role of ∆Np63 in initiating the Wnt signaling in the epidermis and programming the underlying dermal cells and provide new possibilities to harness the intrinsic developmental program for generating the skin and its appendages.

2018-09-05 | GSE102086 | GEO

Single Cell and Open Chromatin Analysis Reveals Molecular Origin of Epidermal Cells of the Skin

2018-09-05 | GSE97213 | GEO

Hair follicle aging is driven by transepidermal stem cell elimination via COL17A1 proteolysis

Project description:Hair loss is one of the typical aging phenotypes in mammals, yet the underlying mechanism(s) is unclear. Here we report that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss both in wild-type mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of Type XVII Collagen (COL17A1/BP180) to trigger “HFSC aging”, characterized by their loss of stemness signature and epidermal commitment. Those aged HFSCs are cyclically eliminated from the skin through their terminal epidermal differentiation, thereby causing hair follicle miniaturization. That process can be recapitulated by Col17a1 deficiency and prevented by forced maintenance of COL17A1 in HFSCs, demonstrating that stem cell homeostasis is the keystone against ultimate execution of the tissue/organ aging program.

2015-12-01 | GSE72863 | GEO

A Microarray-Based Analysis Reveals That A Short Photoperiod Promotes Hair Growth in the Arbas Cashmere Goat

Project description:we evaluated the Arbas Cashmere goat, a species that is especially used in this type of research. The goats were exposed to an experimentally controlled short photoperiod to study the regulation of cyclical cashmere growth. Exposure to a short photoperiod extended the anagen phase of the Cashmere goat hair follicle to increase cashmere production. Based on assessments of tissue sections, it was observed that the short photoperiod significantly induced cashmere growth. A comparison of the differences in gene expression between the short photoperiod and the natural conditions using gene chip technology supported this conclusion. Using the gene chip data, we identified genes that showed altered expression under the short photoperiod compared to natural conditions, and it was found that these genes are involved in the biological processes of hair follicle growth, structural composition of the hair follicle, and the morphogenesis of the surrounding skin appendages.

2015-11-11 | GSE74860 | GEO

Functional stem cell aging dictated by skin tissue microenvironment

Project description:Organismal aging in mammals is manifested with architectural alteration and functional decline of multiple organs throughout the body. In aged skin, hairs are sparse, which has led to the hypothesis that the hair follicle stem cells (HFSCs) undergo epidermal differentiation during aging. Here, we employ single cell analysis to interrogate aging-related changes in the HFSCs. Unexpectedly, HFSCs maintain their lineage fidelity and show no signs of shifting to an epidermal fate. Despite maintaining lineage identity, HFSCs do show prevalent transcriptional changes in extracellular matrix genes. Of importance, these HFSC changes are accompanied by profound architectural perturbations in the aging stem cell niche. Upon surveying the dermis from young and aged skin, we also observe age-related changes in many non-epithelial cell types, including resident immune cells, sensory neurons, arrector pili muscles, and blood vessels – all of which have been previously associated with abilities to modulate hair follicle regeneration. Consistent with both intrinsic and extrinsic alterations in stem cell: niche communications, we find that in response to skin wounding, aged HFSCs repair the epidermis, but are defective in hair follicle regeneration. Intriguingly, whereas aged dermis cannot support young HFSCs, aged HFSCs can be rescued when supported by young dermis. Together, these findings favor a model where skin tissue microenvironment plays a dominant role in dictating the molecular properties and activities of HFSCs.

2019-12-31 | GSE124901 | GEO

Nfatc1 Orchestrates Aging in Hair Follicle Stem Cells

Project description:Mouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by hair follicle stem cells (HFSCs). We used ChIP-seq to unfold genome-wide chromatin landscapes of Nfatc1 and dissect the biological relevence of its upstream BMP signaling in HFSC aging. Telogen quiescent hair follicle stem cells (HFSCs) were FACS-purified for ChIP-sequcencing.

2013-11-14 | E-GEOD-52328 | biostudies-arrayexpress

Calcineurin/Nfatc1 links skin stem cell quiescence to the endocrine hormone prolactin

Project description:Cyclosporine A (CSA) leads to the precocious onset of hair follicle growth, which is driven by premature activation and proliferation of hair follicle stem cells. Here, we identify gene expression changes associated with CSA treatment in hair follicle stem cells prior to the onset of proliferation as a readout for the early events in stem cell actvation. Hair follicle bulge stem cells were FACS-isolated from mouse skin during the 2nd telogen. Two biological replicated were performed.

2013-09-27 | E-GEOD-51194 | biostudies-arrayexpress

RNAseq of scalp biopsies from EGFRi treated patients, who exhibited a folliculitis

Project description:EGFR/MEK inhibitor therapy induces a distinct inflammatory hair follicle response that includes a collapse of hair follicle immune privilege and differential modulation of IL-33 and IL-37 expression. Our findings suggest that successful future management of EGFRi/MEKi-induced folliculitis requires restoration of hair follicle immune privilege. In this RNAseq parietal scalp (rather than truncal skin) biopsies were taken from long-term (3-9 months) EGFRi-treated patients exhibiting folliculitis (Chronic-EGFRi) or from patients prior to commencing and after two weeks of EGFRi therapy (Acute-EGFRi), compared to normal scalp skin.

2024-07-19 | E-MTAB-13455 | biostudies-arrayexpress

SKPs derive from hair follicle precursors and exhibit properties of adult dermal stem cells

Project description:Global expression analysis of neural crest-like skin-derived precursors (SKPs) and Sox2-positive follicle dermal cells that SKPs originate from. In spite of the remarkable regenerative capacity of mammalian skin, an adult dermal stem cell has not yet been identified. Here, we provide evidence that SKPs, multipotent neural crest-like skin-derived precursors, represent an adult dermal stem cell. When transplanted into adult skin, SKPs can reconstitute the adult dermis, contribute to dermal wound-healing, home to a hair follicle niche, and instruct epidermal cells to make hair follicles. Hair follicle-derived SKPs self-renew, maintain their multipotency, and serially reconstitute hair follicles. The endogenous origin of SKPs are Sox2-positive follicle dermal cells that share a similar global gene expression profile with SKPs. These endogenous cells home back to their follicle niche, induce hair follicle morphogenesis, and differentiate into neural and dermal progeny. Hair follicle-associated dermal cells will move out of their niche to contribute to dermal maintenance and wound-healing. These studies therefore identify a dermal stem cell, and provide a biological rationale for the presence of a multipotent precursor within adult dermis, findings with important therapeutic implications.

2009-10-23 | GSE18690 | GEO

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