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

Donega, Vanessa; van der Geest, Astrid T; Sluijs, Jacqueline A; van Dijk, Roland E; Wang, Chi Chiu; Basak, Onur; Pasterkamp, R Jeroen; Hol, Elly M · Nat Commun · 2022

basic_science · Level V

Where this comes from

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<sup>+</sup> 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.

Medical subject headings