Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors.
Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors.
复制标题
DOI：
10.1038/s41467-022-28626-9
复制
发表时间：
2022-02-24
影响因子：
16.6
通讯作者：
Hol EM
中科院分区：
文献类型：
--
作者：
Donega V;van der Geest AT;Sluijs JA;van Dijk RE;Wang CC;Basak O;Pasterkamp RJ;Hol EM
随着出生时神经发生的下降，脑室下区（SVZ）的祖细胞在成年人脑中大多处于静止状态。调节这种静止状态的机制仍然不清楚。在这里，我们从老年人SVZ中分离出CD 271+祖细胞进行单细胞RNA测序分析。我们的转录组数据揭示了老年人SVZ祖细胞的身份，作为晚期少突胶质细胞祖细胞。我们确定Wnt通路拮抗剂SFRP 1作为一个可能的信号，促进静止的祖细胞从老年人SVZ。WAY-316606（一种抑制SFRP 1功能的小分子）的给药在体内和体外稳态条件下刺激神经干细胞的活化。我们的数据揭示了一种可能的机制，通过这种机制，成年人SVZ的祖细胞保持在静止状态，并刺激祖细胞重新激活的潜在目标。出生后神经发生的下降伴随着成年脑神经祖细胞的静止状态特征。在这里，作者将Wnt通路拮抗剂SFRP 1确定为促进静止的潜在信号，并表明其抑制刺激干细胞活化。
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. The decline in neurogenesis following birth is accompanied with a quiescent state characteristic of neural progenitors of the adult brain. Here, the authors identify the Wnt pathway antagonist SFRP1 as a potential signal that promotes quiescence and show that its inhibition stimulates stem cell activation.
登录
查看更多内容
影响因子：
9.8
作者：
Azim K;Angonin D;Marcy G;Pieropan F;Rivera A;Donega V;Cantù C;Williams G;Berninger B;Butt AM;Raineteau O
通讯作者：
Raineteau O
影响因子：
25
作者：
Esteve, Pilar;Rueda-Carrasco, Javier;Bovolenta, Paola
通讯作者：
Bovolenta, Paola
影响因子：
16.2
作者：
Bonnefont, Jerome;Tiberi, Luca;Vanderhaeghen, Pierre
通讯作者：
Vanderhaeghen, Pierre
DOI：
10.1073/pnas.1715911114
发表时间：
2018-01-23
影响因子：
11.1
作者：
Basak, Onur;Krieger, Teresa G.;Clevers, Hans
通讯作者：
Clevers, Hans
影响因子：
16.2
作者：
Bergmann, Olaf;Liebl, Jakob;Frisen, Jonas
通讯作者：
Frisen, Jonas