Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, 3584 CG, Utrecht, The Netherlands.
Department of Obstetrics and Gynecology, 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, Shatin, NT, Hong Kong.
Nat Commun. 2022 Feb 24;13(1):1036. doi: 10.1038/s41467-022-28626-9.
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.
出生后神经发生减少后，侧脑室下区（SVZ）的祖细胞在成人脑中大多处于静止状态。调节这种静止状态的机制尚不清楚。在这里，我们从衰老的人 SVZ 中分离出 CD271 祖细胞进行单细胞 RNA 测序分析。我们的转录组数据揭示了衰老的人 SVZ 祖细胞的身份是晚期少突胶质前体细胞。我们确定 Wnt 通路拮抗剂 SFRP1 是一种可能的信号，可促进衰老的人 SVZ 祖细胞的静止。在体内外，小分子 WAY-316606（一种抑制 SFRP1 功能的小分子）可刺激神经干细胞的激活，而在体内外，这种小分子 WAY-316606（一种抑制 SFRP1 功能的小分子）可刺激神经干细胞的激活，而在体内外，这种小分子 WAY-316606（一种抑制 SFRP1 功能的小分子）可刺激神经干细胞的激活，而在体内外，这种小分子 WAY-316606（一种抑制 SFRP1 功能的小分子）可刺激神经干细胞的激活，而在体内外，这种小分子 WAY-316606（一种抑制 SFRP1 功能的小分子）可刺激神经干细胞的激活。我们的数据揭示了一种可能的机制，通过该机制维持成年 SVZ 祖细胞处于静止状态，并为刺激祖细胞重新激活提供了一个潜在的靶点。
