Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors
Vanessa Donega, Astrid T. van der Geest, Jacqueline A. Sluijs, Roland E. van Dijk, Chi Chiu Wang, Onur Başak, R. Jeroen Pasterkamp, Elly M. Hol
Abstract
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.