Synergistic activation of RARβ and RARγ nuclear receptors restores cell specialization during stem cell differentiation by hijacking RARα-controlled programs.

ABSTRACT: How cells respond to different external cues to develop along defined cell lineages to form complex tissues is a major question in systems biology. Here, we investigated the potential of retinoic acid receptor (RAR)-selective synthetic agonists to activate the gene regulatory programs driving cell specialization during nervous tissue formation from embryonic carcinoma (P19) and mouse embryonic (E14) stem cells. Specifically, we found that the synergistic activation of the RARβ and RARγ by selective ligands (BMS641 or BMS961) induces cell maturation to specialized neuronal subtypes, and to astrocytes and oligodendrocyte precursors. Using RAR isotype knockout lines exposed to RAR-specific agonists, interrogated by global transcriptome landscaping and in silico modeling of transcription regul

SUBMITTER: Koshy A 

PROVIDER: S-EPMC9711859 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature