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

V Donega*, Astrid van der Geest, Jacqueline A. Sluijs, Roland E. van Dijk, Chi-Chiu Wang, Onur Basak, R. Jeroen Pasterkamp, Elly Hol

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number1036
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2022
Externally publishedYes

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