Transcriptional priming as a conserved mechanism of lineage diversification in the developing mouse and human neocortex.

Transcriptional priming as a conserved mechanism of lineage diversification in the developing mouse and human neocortex.
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DOI:
10.1126/sciadv.abd2068
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发表时间:
2020-11
期刊:
影响因子:
13.6
通讯作者:
Haydar TF
Haydar TF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Li Z;Tyler WA;Zeldich E;Santpere Baró G;Okamoto M;Gao T;Li M;Sestan N;Haydar TF

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小鼠和人类皮质祖细胞有着显著的相似性;关键的差异指示物种特异性分化。神经系统中丰富多样的神经元是如何从神经干细胞中产生的还没有很好的理解。使用单细胞RNA测序和体内确认,我们发现了以前未被识别的神经干细胞和祖细胞的多样性在胎鼠和人类新皮层,包括多种类型的放射状胶质细胞和中间祖细胞。我们还观察到,转录引发的基础上的一个子集的心室放射状胶质细胞在这两个物种的多样化;遗传命运映射证实,引发放射状胶质细胞产生特定类型的基底祖细胞和神经元。因此,不同的前体谱系使发育中的小鼠和人类新皮质中的细胞生产流多样化。这些数据表明,转录启动可能是哺乳动物神经前体谱系特化的保守机制。
Mouse and human cortical progenitors share marked similarities; crucial differences instruct species-specific differentiation. How the rich variety of neurons in the nervous system arises from neural stem cells is not well understood. Using single-cell RNA-sequencing and in vivo confirmation, we uncover previously unrecognized neural stem and progenitor cell diversity within the fetal mouse and human neocortex, including multiple types of radial glia and intermediate progenitors. We also observed that transcriptional priming underlies the diversification of a subset of ventricular radial glial cells in both species; genetic fate mapping confirms that the primed radial glial cells generate specific types of basal progenitors and neurons. The different precursor lineages therefore diversify streams of cell production in the developing murine and human neocortex. These data show that transcriptional priming is likely a conserved mechanism of mammalian neural precursor lineage specialization.
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