The circadian regulator PER1 promotes cell reprogramming by inhibiting inflammatory signaling from macrophages.

ABSTRACT: Circadian regulation of gene expression is prevalent and plays critical roles in cell differentiation. However, its roles in the reprogramming of differentiated cells remain largely unknown. Here, we found that one of the master circadian regulators PER1 promoted virus-mediated reprogramming of mouse embryonic fibroblasts (MEFs) to induced neurons (iNs) and induced pluripotent stem cells (iPSCs). Unexpectedly, PER1 achieved this by repressing inflammatory activation of contaminating macrophages in the MEF culture, rather than by directly modulating the reprogrammability of MEFs. More specifically, we found that transduced viruses activated inflammatory genes in macrophages, such as Tnf encoding TNFα, one of the central inflammatory regulators and an autocrine activator of macrophages. TNFα

SUBMITTER: Katoku-Kikyo N 

PROVIDER: S-EPMC10721173 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature