Lineage Commitment of Dermal Fibroblast Progenitors Is Controlled by Kdm6b-Mediated Chromatin Demethylation

August 2023 in “ The EMBO Journal ”

Quan M Phan, Lucia Salz, Sam S Kindl, Jayden S Lopez, Sean Thompson, Jasson Makkar, Iwona M. Driskell, Ryan R. Driskell

dermal fibroblast progenitors Kdm6b chromatin demethylation H3K27me3 epigenetic mechanisms adipocyte compartments dermal papilla

Studysummary This study explored the epigenetic mechanisms of dermal fibroblast progenitor differentiation and found that the repressive chromatin profile from H3K27me3 prevents these progenitors from reforming skin in allograft assays, despite their multipotent potential.

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The study investigates the epigenetic mechanisms controlling the differentiation of Dermal Fibroblast Progenitors (DFPs) into distinct fibroblast lineages during skin development. It was found that DFPs have a repressive chromatin profile, marked by H3K27me3, which limits their ability to reform skin in allograft assays. The research highlights the role of the H3K27me3 demethylase, Kdm6b/Jmjd3, in modulating chromatin derepression. Deleting Kdm6b/Jmjd3 in mice led to the loss of adipocyte compartments and inhibited dermal papilla functions. The study provides insights into the differentiation process of DFPs and introduces a new multiomics search tool.

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