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.

解读人类纹状体是如何发育的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，我们编制了一份包含 1116 个长基因间非编码 RNA (lincRNA) 的目录，从头开始鉴定，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-MSNs）来自一个共同的祖细胞，并且在有丝分裂后过渡期间建立了谱系承诺，跨越一个显示连续命运决定因素谱的前 MSN 阶段。然后，我们发现了我们通过计算机扰动验证的细胞类型特异性基因调控网络。最后，我们确定了人类特异性 lincRNA，这些 lincRNA 有助于人类这种结构的系统发育差异。