The coding and long noncoding single-cell atlas of the developing human fetal striatum
The coding and long noncoding single-cell atlas of the developing human fetal striatum
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DOI：
10.1126/science.abf5759
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发表时间：
2021-05-07
期刊：
影响因子：
56.9
通讯作者：
Cattaneo, Elena
中科院分区：
文献类型：
--
作者：
Bocchi, Vittoria Dickinson;Conforti, Paola;Cattaneo, Elena
解读人类纹状体的发育方式对于了解影响该区域的疾病是必要的。为了解码在发育过程中调节这种结构的转录模块，我们编辑了一个1116个从头鉴定的长基因间非编码RNA（lincRNA）的目录，然后分析了来自早期人类胎儿纹状体的96，789个单细胞。我们发现，D1和D2中型多刺神经元（D1-和D2-MSN）来自一个共同的祖细胞和谱系承诺建立在有丝分裂后的过渡，在前MSN阶段，表现出连续的频谱的命运决定因素。然后，我们发现了细胞类型特异性的基因调控网络，我们通过计算机微扰验证。最后，我们鉴定了人类特异性lincRNA，其有助于该结构在人类中的系统发育分歧。这项工作描绘了细胞层次结构管理MSN血统的承诺。
Deciphering how the human striatum develops is necessary for understanding the diseases that affect this region. To decode the transcriptional modules that regulate this structure during development, we compiled a catalog of 1116 long intergenic noncoding RNAs (lincRNAs) identified de novo and then profiled 96,789 single cells from the early human fetal striatum. We found that D1 and D2 medium spiny neurons (D1- and D2-MSNs) arise from a common progenitor and that lineage commitment is established during the postmitotic transition, across a pre-MSN phase that exhibits a continuous spectrum of fate determinants. We then uncovered cell type-specific gene regulatory networks that we validated through in silico perturbation. Finally, we identified human-specific lincRNAs that contribute to the phylogenetic divergence of this structure in humans. This work delineates the cellular hierarchies governing MSN lineage commitment.