Paired Related Homeobox Protein 1 Regulates Quiescence in Human Oligodendrocyte Progenitors

Cell Rep. 2018 Dec 18;25(12):3435-3450.e6. doi: 10.1016/j.celrep.2018.11.068.


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 G1/0 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.

Keywords: RNA-seq; RNAi; glia; human; quiescence.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / pharmacology
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle* / drug effects
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Demyelinating Diseases / metabolism
  • Demyelinating Diseases / pathology
  • Gene Expression Regulation / drug effects
  • Homeodomain Proteins / metabolism*
  • Humans
  • Interferon-gamma / pharmacology
  • Ki-67 Antigen / metabolism
  • Mice
  • Myelin Sheath / metabolism
  • Oligodendrocyte Precursor Cells / cytology*
  • Oligodendrocyte Precursor Cells / metabolism*
  • Oligodendrocyte Precursor Cells / transplantation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Up-Regulation / drug effects
  • White Matter / metabolism
  • White Matter / pathology


  • Bone Morphogenetic Proteins
  • Homeodomain Proteins
  • Ki-67 Antigen
  • PRRX1 protein, human
  • RNA, Messenger
  • Interferon-gamma