Similar Datasets
Project description:Aging is defined as the functional decline of tissues and organisms, leading to many human conditions, such as cancer, neurodegenerative diseases, and hair loss. Although stem cell exhaustion is widely recognized as a hallmark of aging, our understanding of cell state changes-specifically, the dynamics of the transcriptome and open chromatin landscape, and their relationship with aging-remains incomplete. Here we present a longitudinal, single-cell atlas of the transcriptome and open chromatin landscape for epithelia cells of the skin across various hair cycle stages and ages in mice. Our findings reveal fluctuating hair follicle stem cell (HF-SC) states, some of which are associated with the progression of the hair cycle during aging. Conversely, inner bulge niche cells display a more linear progression, seemingly less affected by the hair cycle. Further analysis of the open chromatin landscape, determined by single-cell Assay for Transposase-Accessible Chromatin (ATAC) sequencing, demonstrates that reduced open chromatin regions in HF-SCs are associated with differentiation, whereas gained open chromatin regions in HF-SCs are linked to the transcriptional control of quiescence. These findings enhance our understanding of the transcriptional dynamics in HF-SC aging and lay the molecular groundwork for investigating and potentially reversing the aging process in future experimental studies.
| S-EPMC10350644 | biostudies-literature
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
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 | GSE227782 | GEO
Project description:Single cell analysis of transcriptome and open chromatin reveals the dynamics of hair follicle stem cell aging
| PRJNA946816 | ENA
Project description:Multipotent bulge stem cells (SCs) fuel the hair follicle (HF) cyclic growth during adult skin homeostasis, but their intrinsic molecular heterogeneity is not well understood. These hair follicle stem cells (HFSCs) engage in bouts of self-renewal, migration and differentiation during the hair cycle. Here, we perform high-resolution single-cell RNA sequencing (scRNA-seq) of HFSCs sorted as CD34+ /K14-H2BGFP+ from mouse skin at mid-anagen, the self-renewal stage. We dissect the transcriptomic profiles and unravel population-specific transcriptional heterogeneity. Unsupervised clustering reveals five major HFSC populations, which distinguished by known markers associated with both the bulge and the outer root sheath (ORS) underneath. These populations include quiescent bulge, ORS cellular states and proliferative cells. Lineage trajectory analysis predicted the prospective differentiation path of these cellular states and their corresponding self-renewing subpopulations. The bulge population itself can be further sub-divided into distinct subpopulations that can be mapped to the upper, mid and lower bulge regions, and present a decreasing quiescence score. Gene set enrichment analysis (GSEA) revealed new markers and suggested potentially distinct functions of the ORS and bulge subpopulations. This included communications between the upper bulge subpopulation and sensory nerves and between the upper ORS and skin vasculature, as well as enrichment of a bulge subset in cell migratory functions. The lower ORS enriched genes may potentially enable nutrients passing from the surrounding fat and vasculature cells towards the proliferating hair matrix cells. Thus, we provide a comprehensive account of HFSC molecular heterogeneity during their self-renewing stage, which enables future HF functional studies.
| S-EPMC8016723 | biostudies-literature
Project description:Single cell analysis of transcriptome and open chromatin reveals the dynamics of hair follicle stem cell aging [scRNA-Seq]
| PRJNA946878 | ENA
Project description:Single cell analysis of transcriptome and open chromatin reveals the dynamics of hair follicle stem cell aging [scATAC-Seq]
| PRJNA946879 | ENA
Project description:Hair production is fueled by stem cells (SCs), which transition between cyclical bouts of rest and activity. Here, we explore why hair growth wanes with age. We show that aged hair follicle SCs (HFSCs) in mice exhibit enhanced resting and abbreviated growth phases and are delayed in response to tissue-regenerating cues. Aged HFSCs are poor at initiating proliferation and show diminished self-renewing capacity upon extensive use. Only modestly restored by parabiosis, these features are rooted in elevated cell-intrinsic sensitivity and local elevation in bone morphogenic protein (BMP) signaling. Transcriptional profiling presents differences consistent with defects in aged HFSC activation. Notably, BMP-/calcium-regulated, nuclear factor of activated T-cell c1 (NFATc1) in HFSCs becomes recalcitrant to its normal down-regulating cues, and NFATc1 ChIP-sequencing analyses reveal a marked enrichment of NFATc1 target genes within the age-related signature. Moreover, aged HFSCs display more youthful levels of hair regeneration when BMP and/or NFATc1 are inhibited. These results provide unique insights into how skin SCs age.
| S-EPMC3870727 | biostudies-literature
Project description:Tissue regeneration relies on resident stem cells (SCs), whose activity and lineage choices are influenced by the microenvironment. Exploiting the synchronized, cyclical bouts of tissue regeneration in hair follicles (HFs), we investigate how microenvironment dynamics shape the emergence of stem cell lineages. Employing epigenetic and ChIP-seq profiling, we uncover how signal-dependent transcription factors couple spatiotemporal cues to chromatin dynamics, thereby choreographing stem cell lineages. Using enhancer-driven reporters, mutagenesis, and genetics, we show that simultaneous BMP-inhibitory and WNT signals set the stage for lineage choices by establishing chromatin platforms permissive for diversification. Mechanistically, when binding of BMP effector pSMAD1 is relieved, enhancers driving HF-stem cell master regulators are silenced. Concomitantly, multipotent, lineage-fated enhancers silent in HF-stem cells become activated by exchanging WNT effectors TCF3/4 for LEF1. Throughout regeneration, lineage enhancers continue reliance upon LEF1 but then achieve specificity by accommodating additional incoming signaling effectors. Barriers to progenitor plasticity increase when diverse, signal-sensitive transcription factors shape LEF1-regulated enhancer dynamics.
| S-EPMC6425486 | biostudies-literature
Project description:BackgroundWound-induced hair follicle neogenesis (WIHN) is a phenomenon of hair neogenesis that occurs at the center of a scar when the wound area is sufficiently large. Neogenic hair follicles are separated from the pre-existing follicles at the wound edge by a hairless circular region. This WIHN study provides a unique model for developing treatments for hair loss and deciphering the mechanisms underlying organogenesis in adult mammals.MethodsThe skin of a mouse was wounded by excising a 1.5 × 1.5 cm2 square of full-thickness dorsal skin. iTRAQ technology was used to screen proteins differentially expressed between the inner and outer scar areas in a mouse model of WIHN, on post-wounding day 15, to identify the regulators of WIHN. Owing to the overexpression of interleukin-36α (IL-36α) in the de novo hair follicle growth area, the regulating effect of IL-36α overexpression in WIHN was investigated. Hair follicle stem/progenitor cells were counted by flow cytometry while the expression of hair follicle stem/progenitor cell markers (Lgr5, Lgr6, Lrig1, K15, and CD34) and that of Wnt/β-catenin and IL-6/STAT3 pathway intermediaries was detected by qPCR and western blotting.ResultsWe found that wounding induced IL-36α expression. Incorporation of recombinant murine IL-36α (mrIL-36α) into murine skin wounds resulted in a greater number of regenerated hair follicles (p < 0.005) and a faster healing rate. The expression of hair follicle stem/progenitor cell markers was upregulated in the mrIL-36α-injected site (p < 0.05). Additionally, mrIL-36α upregulated the IL-6/STAT3 pathway intermediaries.ConclusionIL-36α is upregulated in de novo hair follicle growth areas and can promote wound epithelialization and WIHN.
| S-EPMC7493638 | biostudies-literature