High‐resolution single‐cell transcriptomics reveals heterogeneity of self‐renewing hair follicle stem cells

Chovatiya, Gopal; Ghuwalewala, Sangeeta; Walter, Lauren D.; Cosgrove, Benjamin D.; Tumbar, Tudorita

doi:10.1111/exd.14262

Cited by 28 publications

(29 citation statements)

References 66 publications

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“…2c ), suggesting that they have different differentiation tendency. When compared with previously characterized mHFSC subgroups via scRNA-seq 18 , the S3 group was specifically enriched for migrating bulge (migroBulge) signature genes (Fig. 2d , Supplementary Table S4 ), implicating that it represented HFSCs migrating out of their niche.…”

Section: Resultsmentioning

confidence: 94%

Single-cell transcriptomics reveals lineage trajectory of human scalp hair follicle and informs mechanisms of hair graying

Liu

et al. 2022

Cell Discov

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Hair conditions, such as hair loss and graying, are prevalent human conditions. But they are often poorly controlled due to our insufficient understanding of human scalp hair follicle (hsHF) in health and disease. Here we describe a comprehensive single-cell RNA-seq (scRNA-seq) analysis on highly purified black and early-stage graying hsHFs. Based on these, a concise single-cell atlas for hsHF and its early graying changes is generated and verified using samples from multiple independent individuals. These data reveal the lineage trajectory of hsHF in unprecedented detail and uncover its multiple unexpected features not found in mouse HFs, including the presence of an innerbulge like compartment in the growing phase, lack of a discrete companion layer, and enrichment of EMT features in HF stem cells (HFSCs). Moreover, we demonstrate that besides melanocyte depletion, early-stage human hair graying is also associated with specific depletion of matrix hair progenitors but not HFSCs. The hair progenitors’ depletion is accompanied by their P53 pathway activation whose pharmaceutical blockade can ameliorate hair graying in mice, enlightening a promising therapeutic avenue for this prevalent hair condition.

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Section: Resultsmentioning

confidence: 94%

Single-cell transcriptomics reveals lineage trajectory of human scalp hair follicle and informs mechanisms of hair graying

Liu

et al. 2022

Cell Discov

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“…Powered by single-cell RNA sequencing (scRNA-seq), the above problems could be well solved now. Single-cell gene expression studies enable one to profile transcriptional regulation in highly heterogeneous cell populations and complex biological processes (Chovatiya et al, 2021), which was applied in hair follicle biology researches (Joost et al, 2016;Ge et al, 2020;Haensel et al, 2020;Takahashi et al, 2020;Ge et al, 2021). Recently, Joost et al used scRNA-seq to reveal unprecedented molecular details of cell types and states coordinating hair growth in mice (Joost et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Transcriptomics Reveals the Molecular Anatomy of Sheep Hair Follicle Heterogeneity and Wool Curvature

Wang¹,

Wu²,

Sun³

et al. 2021

Front. Cell Dev. Biol.

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Wool is the critical textile raw material which is produced by the hair follicle of sheep. Therefore, it has important implications to investigate the molecular mechanism governing hair follicle development. Due to high cellular heterogeneity as well as the insufficient cellular, molecular, and spatial characterization of hair follicles on sheep, the molecular mechanisms involved in hair follicle development and wool curvature of sheep remains largely unknown. Single-cell RNA sequencing (scRNA-seq) technologies have made it possible to comprehensively dissect the cellular composition of complex skin tissues and unveil the differentiation and spatial signatures of epidermal and hair follicle development. However, such studies are lacking so far in sheep. Here, single-cell suspensions from the curly wool and straight wool lambskins were prepared for unbiased scRNA-seq. Based on UAMP dimension reduction analysis, we identified 19 distinct cell populations from 15,830 single-cell transcriptomes and characterized their cellular identity according to specific gene expression profiles. Furthermore, novel marker gene was applied in identifying dermal papilla cells isolated in vitro. By using pseudotime ordering analysis, we constructed the matrix cell lineage differentiation trajectory and revealed the dynamic gene expression profiles of matrix progenitors' commitment to the hair shaft and inner root sheath (IRS) cells. Meanwhile, intercellular communication between mesenchymal and epithelial cells was inferred based on CellChat and the prior knowledge of ligand–receptor pairs. As a result, strong intercellular communication and associated signaling pathways were revealed. Besides, to clarify the molecular mechanism of wool curvature, differentially expressed genes in specific cells between straight wool and curly wool were identified and analyzed. Our findings here provided an unbiased and systematic view of the molecular anatomy of sheep hair follicle comprising 19 clusters; revealed the differentiation, spatial signatures, and intercellular communication underlying sheep hair follicle development; and at the same time revealed the potential molecular mechanism of wool curvature, which will give important new insights into the biology of the sheep hair follicle and has implications for sheep breeding.

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“…We elected to use a nuclear H2B-GFP we and others have previously used 2,20,21 . The H2B-GFP sequence was inserted into exon 1 of one LGR5 allele and after validation for accurate transgene insertion by PCR and sequencing (Fig.…”

Section: Generation Of a Porcine Lgr5-h2b-gfp Modelmentioning

confidence: 99%

LGR5 is a Conserved Marker of Hair Follicle Stem Cells Across Species and is Present Early and Throughout Follicle Morphogenesis

Polkoff

Gupta

Green

et al. 2022

Preprint

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Hair follicle stem cells are key for driving growth and homeostasis of the hair follicle niche and have remarkable regenerative capacity throughout hair cycling and display fate plasticity during cutaneous wound healing. Due to the need for a transgenic reporter, essentially all observations related to LGR5+ hair follicle stem cells have been generated using transgenic mice, which have significant differences in anatomy and physiology from the human. Using a transgenic pig model, a widely accepted model for human skin and human skin repair, we demonstrate that LGR5 is a marker of hair follicle stem cells across species in homeostasis and development. We also report the strong similarities and important differences in expression patterns, gene expression profiles, and developmental processes between species. This information is important for understanding the fundamental differences and similarities across species, and ultimately improving human hair follicle regeneration, cutaneous wound healing, and skin cancer treatment.

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High‐resolution single‐cell transcriptomics reveals heterogeneity of self‐renewing hair follicle stem cells

Cited by 28 publications

References 66 publications

Single-cell transcriptomics reveals lineage trajectory of human scalp hair follicle and informs mechanisms of hair graying

Single-cell transcriptomics reveals lineage trajectory of human scalp hair follicle and informs mechanisms of hair graying

Single-Cell Transcriptomics Reveals the Molecular Anatomy of Sheep Hair Follicle Heterogeneity and Wool Curvature

LGR5 is a Conserved Marker of Hair Follicle Stem Cells Across Species and is Present Early and Throughout Follicle Morphogenesis

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