Coordinated inhibition of SOX9 and cell-cycle progression by microRNA-200 restricts sebaceous gland fate specification
Abstract
The microRNA-200 family (miR-200s) is known for inhibiting epithelial-to-mesenchymal transition and cell-cycle progression in cancer, but its function in epithelial development remains unclear. Here we show that miR-200s are highly enriched in hair matrix progenitors but absent from the upper hair follicle (HF), where sebaceous gland (SG) and HF stem cells are specified. Ectopic miR-200 induction abolishes SG specification while preserving hair morphogenesis. Genome-wide identification of miR-200 targets reveals direct repression of negative regulators of WNT signaling and cell-cycle regulators. Single-cell and spatial transcriptomic analyses uncover mutually exclusive domains of WNT activity and SOX9 expression in the upper HF that is disrupted by miR-200 induction. Genome-wide mapping of SOX9 targets further uncovers a lipogenic and fatty-acid metabolic program required for SG specification. Together, these findings show that miR-200 blocks SG fate by inhibiting SOX9 function and restricting cell proliferation, defining a spatially organized regulatory network essential for SG development.
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BibTeX
@article{das2026coordinated,
title = {{Coordinated inhibition of SOX9 and cell-cycle progression by microRNA-200 restricts sebaceous gland fate specification}},
author = {Arpan Das and Yuheng C. Fu and Haimin Li and Megan A. Wong and Annalina Che and Anumeha Singh and Jimin Han and Glen Bjerke and Dongmei Wang and Rui Yi},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-77136-5},
url = {https://www.nature.com/articles/s41467-026-77136-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Coordinated inhibition of SOX9 and cell-cycle progression by microRNA-200 restricts sebaceous gland fate specification
AU - Arpan Das
AU - Yuheng C. Fu
AU - Haimin Li
AU - Megan A. Wong
AU - Annalina Che
AU - Anumeha Singh
AU - Jimin Han
AU - Glen Bjerke
AU - Dongmei Wang
AU - Rui Yi
PY - 2026
DA - 2026/10/16
JO - Nature Communications
DO - 10.1038/s41467-026-77136-5
UR - https://www.nature.com/articles/s41467-026-77136-5
AB - The microRNA-200 family (miR-200s) is known for inhibiting epithelial-to-mesenchymal transition and cell-cycle progression in cancer, but its function in epithelial development remains unclear. Here we show that miR-200s are highly enriched in hair matrix progenitors but absent from the upper hair follicle (HF), where sebaceous gland (SG) and HF stem cells are specified. Ectopic miR-200 induction abolishes SG specification while preserving hair morphogenesis. Genome-wide identification of miR-200 targets reveals direct repression of negative regulators of WNT signaling and cell-cycle regulators. Single-cell and spatial transcriptomic analyses uncover mutually exclusive domains of WNT activity and SOX9 expression in the upper HF that is disrupted by miR-200 induction. Genome-wide mapping of SOX9 targets further uncovers a lipogenic and fatty-acid metabolic program required for SG specification. Together, these findings show that miR-200 blocks SG fate by inhibiting SOX9 function and restricting cell proliferation, defining a spatially organized regulatory network essential for SG development.
SN - 2041-1723
ER -