Loss of PRC1 activity in different stem cell compartments activates a common transcriptional program with cell type-dependent outcomes

不同干细胞区室中 PRC1 活性的丧失会激活一个具有细胞类型依赖性结果的常见转录程序

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作者:Silvia Pivetti, Daniel Fernandez-Perez, Alessandro D'Ambrosio, Caterina Maria Barbieri, Daria Manganaro, Alessandra Rossi, Laura Barnabei, Marika Zanotti, Andrea Scelfo, Fulvio Chiacchiera, Diego Pasini

Abstract

Polycomb repressive complexes are evolutionarily conserved complexes that maintain transcriptional repression during development and differentiation to establish and preserve cell identity. We recently described the fundamental role of PRC1 in preserving intestinal stem cell identity through the inhibition of non-lineage-specific transcription factors. To further elucidate the role of PRC1 in adult stem cell maintenance, we now investigated its role in LGR5+ hair follicle stem cells during regeneration. We show that PRC1 depletion severely affects hair regeneration and, different from intestinal stem cells, derepression of its targets induces the ectopic activation of an epidermal-specific program. Our data support a general role of PRC1 in preserving stem cell identity that is shared between different compartments. However, the final outcome of the ectopic activation of non-lineage-specific transcription factors observed upon loss of PRC1 is largely context-dependent and likely related to the transcription factors repertoire and specific epigenetic landscape of different cellular compartments.

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