An Integrated Transcriptome Atlas of Embryonic Hair Follicle Progenitors, Their Niche, and the Developing Skin
Open accessAbstract
Defining the unique molecular features of progenitors and their niche requires a genome-wide, whole-tissue approach with cellular resolution. Here, we co-isolate embryonic hair follicle (HF) placode and dermal condensate cells, precursors of adult HF stem cells and the dermal papilla/sheath niche, along with lineage-related keratinocytes and fibroblasts, Schwann cells, melanocytes, and a population inclusive of all remaining skin cells. With next-generation RNA sequencing, we define gene expression patterns in the context of the entire embryonic skin, and through transcriptome cross-comparisons, we uncover hundreds of enriched genes in cell-type-specific signatures. Axon guidance signaling and many other pathway genes are enriched in multiple signatures, implicating these factors in driving the large-scale cellular rearrangements necessary for HF formation. Finally, we share all data in an interactive, searchable companion website. Our study provides an overarching view of signaling within the entire embryonic skin and captures a molecular snapshot of HF progenitors and their niche.
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In day-48 WA25 organoids, five VIM+ clusters contained cells expressing DPT, TWIST2 and LUM, as well as numerous collagen genes, such as COL1A1/2, COL3A1, COL5A3, COL6A3, COL12A1, and COL21A1.
“In particular, five VIM+ clusters contained cells expressing DPT, TWIST2 and LUM, as well as numerous collagen genes, such as COL1A1/2, COL3A1, COL5A3, COL6A3, COL12A1, and COL21A1 (Extended Data Fig. 6a–d, see Supplementary Data 7 for detailed analysis)24.”
From Hair-bearing human skin generated entirely from pluripotent stem cells (2020) · cites this paper as [24]
In Results, under “Isolation of HF Placode Progenitors, Dermal Condensate Niche Cells, and other Distinct Cell Types from Embryonic Skin” (page unavailable), the source identifies Col1a1 as a fibroblast marker. It does not report day-48 WA25 organoids, five VIM+ clusters, or the full list of genes attributed to those clusters; those are findings referenced to the citing paper’s own figure and supplementary data. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe mesenchymal group contained ten distinct PRRX1+ populations, including dermal fibroblast-like subtypes expressing TRIL, TWIST2, APCDD1, and PAX1.
“The mesenchymal group contained ten distinct PRRX1+ populations, including dermal fibroblast-like subtypes expressing TRIL, TWIST2, APCDD1, and PAX1 (Fig. 2h, Extended Data Fig. 5)24.”
From Hair-bearing human skin generated entirely from pluripotent stem cells (2020) · cites this paper as [24]
The Results section on cell isolation reports dermal fibroblast cells, and the section on established gene markers notes heterogeneity in embryonic fibroblasts. Our copy does not report ten PRRX1+ mesenchymal populations or fibroblast-like subtypes expressing TRIL, TWIST2, APCDD1, and PAX1; searches for those terms returned no supporting passage. Page numbers were not available in the indexed copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredAtoh-1 is expressed by hair-follicle stem cells and progenitors, and by embryonic melanocytes and placode cells.
“Atoh-1 gene was previously shown to be expressed by hair-follicle stem cells and progenitors, and by embryonic melanocytes and placode cells [2,34,35].”
From Efficient Generation of Skin Organoids from Pluripotent Cells via Defined Extracellular Matrix Cues and Morphogen Gradients in a Spindle‐Shaped Microfluidic Device (2024) · cites this paper as [34]
The Results sections describe embryonic placode progenitors and melanocytes and identify other genes expressed in those cells, but the passages do not identify Atoh-1 as one of them. Searches for Atoh1, Atoh-1, and atonal homolog 1 found no passage addressing its expression; page numbers are unavailable in our copy. (LLM, conf=0.72)
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References 54 · Cited by 211
Research works printed but not linked: 48
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- Authors
- Sennett, R., Wang, Z., Rezza, A., Grisanti, L., Roitershtein, N., Sicchio, C., Mok, K. W., Heitman, N. J., Clavel, C., Ma’ayan, A., & Rendl, M.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Rendl, Michael
- ORCID
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 34
- Issue
- 5
- Pages
- 577-591
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC4573840
- OpenAlex
- W1828641238
- Cited by
- 211
- References
- 54
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 17 · 2023: 25 · 2022: 29 · 2021: 21 · 2020: 20 · 2019: 20 · 2018: 25 · 2017: 14 · 2016: 9 · 2015: 1
- FWCI
- 21.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (U54HL127624)
- National Cancer Institute (U54CA189201)
- National Institute of General Medical Sciences (R01GM098316)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK088541)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR063151, R01AR059143, F30AR065847)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- dermal papilla, skin development, transcriptome atlas, axon guidance signaling, hair follicle stem cells, keratinocytes, fibroblasts, Schwann cells, melanocytes, placodes
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Skin, Stem Cells, Signal Transduction, Keratinocytes, Hair Follicle, Organogenesis, Mice, Stem Cell Niche, Transcriptome
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