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

Author

Listed:
  • 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
    Charite-University Medicine Berlin)

  • 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)

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.

Suggested Citation

  • Vanessa Donega & Astrid T. Geest & Jacqueline A. Sluijs & Roland E. Dijk & Chi Chiu Wang & Onur Basak & R. Jeroen Pasterkamp & Elly M. Hol, 2022. "Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28626-9
    DOI: 10.1038/s41467-022-28626-9
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    References listed on IDEAS

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    1. Suijuan Zhong & Shu Zhang & Xiaoying Fan & Qian Wu & Liying Yan & Ji Dong & Haofeng Zhang & Long Li & Le Sun & Na Pan & Xiaohui Xu & Fuchou Tang & Jun Zhang & Jie Qiao & Xiaoqun Wang, 2018. "A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex," Nature, Nature, vol. 555(7697), pages 524-528, March.
    2. Nader Sanai & Thuhien Nguyen & Rebecca A. Ihrie & Zaman Mirzadeh & Hui-Hsin Tsai & Michael Wong & Nalin Gupta & Mitchel S. Berger & Eric Huang & Jose-Manuel Garcia-Verdugo & David H. Rowitch & Arturo , 2011. "Corridors of migrating neurons in the human brain and their decline during infancy," Nature, Nature, vol. 478(7369), pages 382-386, October.
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