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.
(2022) Nature Communications, volume 13, issue 1, pp. 1 - 12
(Article)
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
... read more
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.
show less
Download/Full Text
Keywords: Aged, Brain/metabolism, Cell Differentiation/genetics, Humans, Intercellular Signaling Peptides and Proteins/metabolism, Lateral Ventricles/metabolism, Membrane Proteins/genetics, Neural Stem Cells/metabolism, Neurogenesis/genetics, Transcriptome, General Physics and Astronomy, General Chemistry, General Biochemistry,Genetics and Molecular Biology, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 2041-1723
Publisher: Nature Publishing Group
Note: Funding Information: This work was supported by an Off-road grant (04510011910009) to V.D, a TAS-ZonMw grant (40-41400-98-16020) to E.M.H., by the MAXOMOD consortium, under the frame of E-Rare-3, the ERANET for Research on Rare Diseases (ERARE18-070) to R.J.P., and a Ministry of Science and Technology of China (MOST, 2016YFC1000500), a Theme-based Research Scheme (TRS, T13-602/21-N), a Health and Medical Research Fund (01120156) and CUHK Direct Grant (2019.052) to C.C.W. We are grateful to Peter Burbach for discussions and comments on the manuscript. We thank Christiaan van der Meer, Youri Adolfs, Roger Koot, and Nina Chu for technical support. The single-cell RNA sequencing was performed at Single Cell Discoveries by Judith Vivié and Mauro Muraro. Publisher Copyright: © 2022, The Author(s).
(Peer reviewed)
