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

Vanessa Donega (), Astrid T. Geest, Jacqueline A. Sluijs, Roland E. Dijk, Chi Chiu Wang, Onur Basak, R. Jeroen Pasterkamp and Elly M. Hol ()
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Vanessa Donega: University Medical Center Utrecht, Utrecht University
Astrid T. Geest: University Medical Center Utrecht, Utrecht University
Jacqueline A. Sluijs: University Medical Center Utrecht, Utrecht University
Roland E. Dijk: University Medical Center Utrecht, Utrecht University
Chi Chiu Wang: Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences, and Chinese University of Hong Kong -Sichuan University Joint Laboratory in Reproductive Medicine, The Chinese University of Hong Kong
Onur Basak: University Medical Center Utrecht, Utrecht University
R. Jeroen Pasterkamp: University Medical Center Utrecht, Utrecht University
Elly M. Hol: University Medical Center Utrecht, Utrecht University

Nature Communications, 2022, vol. 13, issue 1, 1-12

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.

Date: 2022
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DOI: 10.1038/s41467-022-28626-9

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