Pluto Biosciences, Inc

GSE122563: Paired Related Homeobox Protein 1 Regulates Quiescence in Human Oligodendrocyte Progenitors

Bulk RNA sequencing

Human oligodendrocyte progenitor cells (hOPCs) persist into adulthood as an abundant precursor population of capable of division and differentiation. The transcriptional mechanisms that regulate hOPC homeostasis remain poorly defined. Herein, we identified paired related homeobox protein 1 (PRRX1) in primary PDGFaR+ hOPCs. We show that enforced PRRX1 expression resulted in reversible G0/1 arrest. While both PRRX1 splice variants reduced hOPC proliferation, only PRRX1a abrogated migration. hOPCs engraftment into hypomyelinated shiverer/rag2 mouse brain was severely impaired by PRRX1a, characterized by reduced cell proliferation and migration. PRRX1 induced a gene expression signature characteristic of stem cell quiescence. Both IFN-g and BMP signaling up-regulated PRRX1 and induced quiescence. Importantly, PRRX1 knockdown modulated IFN-g induced quiescence. In mouse brain, PRRX1 mRNA was detected in non-dividing OPCs and was up-regulated in OPCs following demyelination. Together, these data identify PRRX1 as a regulator of quiescence in hOPCs and as a potential regulator of pathological quiescence. SOURCE: Fraser,James,Sim (fjsim@buffalo.edu) - University at Buffalo

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