Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors

Nat Commun. 2022 Feb 24;13(1):1036. doi: 10.1038/s41467-022-28626-9.


Following the decline of neurogenesis at birth, progenitors of the subventricular zone (SVZ) remain mostly in a quiescent state in the adult human brain. The mechanisms that regulate this quiescent state are still unclear. Here, we isolate CD271+ progenitors from the aged human SVZ for single-cell RNA sequencing analysis. Our transcriptome data reveal the identity of progenitors of the aged human SVZ as late oligodendrocyte progenitor cells. We identify the Wnt pathway antagonist SFRP1 as a possible signal that promotes quiescence of progenitors from the aged human SVZ. Administration of WAY-316606, a small molecule that inhibits SFRP1 function, stimulates activation of neural stem cells both in vitro and in vivo under homeostatic conditions. Our data unravel a possible mechanism through which progenitors of the adult human SVZ are maintained in a quiescent state and a potential target for stimulating progenitors to re-activate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain / metabolism
  • Cell Differentiation / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lateral Ventricles* / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Neural Stem Cells* / metabolism
  • Neurogenesis / genetics
  • Transcriptome


  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • SFRP1 protein, human