AI Article Synopsis
- Human oligodendrocyte progenitor cells (hOPCs) are important for brain health and can divide and differentiate into other cell types, but the mechanisms controlling their behavior are not well understood.
- Researchers have identified paired related homeobox protein 1 (PRRX1) as a key player in regulating the growth and movement of hOPCs, with specific splice variants affecting their proliferation and migration.
- PRRX1 is linked to a state of quiescence (a sort of cellular "resting" state) and is influenced by signaling molecules like IFN-γ and BMP, suggesting it could play a significant role in both normal and pathological brain conditions.
Article Abstract
Human oligodendrocyte progenitor cells (hOPCs) persist into adulthood as an abundant precursor population capable of division and differentiation. The transcriptional mechanisms that regulate hOPC homeostasis remain poorly defined. Herein, we identify paired related homeobox protein 1 (PRRX1) in primary PDGFαR hOPCs. We show that enforced PRRX1 expression results in reversible G arrest. While both PRRX1 splice variants reduce hOPC proliferation, only PRRX1a abrogates migration. hOPC engraftment into hypomyelinated shiverer/rag2 mouse brain is severely impaired by PRRX1a, characterized by reduced cell proliferation and migration. PRRX1 induces a gene expression signature characteristic of stem cell quiescence. Both IFN-γ and BMP signaling upregulate PRRX1 and induce quiescence. PRRX1 knockdown modulates IFN-γ-induced quiescence. In mouse brain, PRRX1 mRNA was detected in non-dividing OPCs and is upregulated in OPCs following demyelination. Together, these data identify PRRX1 as a regulator of quiescence in hOPCs and as a potential regulator of pathological quiescence.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347430 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2018.11.068 | DOI Listing |
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