An atlas of late prenatal human neurodevelopment resolved by single-nucleus transcriptomics.
An atlas of late prenatal human neurodevelopment resolved by single-nucleus transcriptomics.
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DOI：
10.1038/s41467-022-34975-2
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发表时间：
2022-12-12
影响因子：
16.6
通讯作者：
Tsankova, Nadejda M.
中科院分区：
文献类型：
--
作者：
Ramos, Susana, I;Mussa, Zarmeen M.;Falk, Elisa N.;Pai, Balagopal;Giotti, Bruno;Allette, Kimaada;Cai, Peiwen;Dekio, Fumiko;Sebra, Robert;Beaumont, Kristin G.;Tsankov, Alexander M.;Tsankova, Nadejda M.
人类新皮质的产前晚期发育包括胶质生成和皮质扩张的关键时期。然而，缺乏系统的单细胞分析来解决妊娠晚期的细胞多样性和胶质细胞谱系。在这里，我们展示了一份全面的单核 RNA 测序图谱，其中包含超过 200,000 个细胞核，这些细胞核来自 15 个 17 至 41 孕周的产前、非病理性尸检样本和 3 个成人对照的增殖生发基质和层压皮质板。该数据集以高时间分辨率捕获产前胶质细胞生成，并作为进一步询问的资源提供。我们的计算分析解决了神经胶质祖细胞的更大复杂性，包括人类妊娠晚期的瞬时神经胶质中间祖细胞（gIPC）和新生星形胶质细胞群。我们使用谱系轨迹和 RNA 速度推断来进一步表征少突胶质细胞 (gIPC-O) 和星形胶质细胞 (gIPC-A) 谱系分化之前的特定 gIPC 亚群。我们推断出与每种发育状态相关的独特转录驱动因素和生物途径，验证人类生发基质和皮质板中 gIPC-A 和 gIPC-O 的存在，并证明 gIPC 状态在成人和儿童胶质母细胞瘤肿瘤中得到重现。人类新皮质的产前晚期发育包括胶质生成和皮质扩张的关键时期。在这里，作者使用人类转录组学来捕获产前发育中后期细胞的短暂性和多样性，包括神经胶质祖细胞特征。
Late prenatal development of the human neocortex encompasses a critical period of gliogenesis and cortical expansion. However, systematic single-cell analyses to resolve cellular diversity and gliogenic lineages of the third trimester are lacking. Here, we present a comprehensive single-nucleus RNA sequencing atlas of over 200,000 nuclei derived from the proliferative germinal matrix and laminating cortical plate of 15 prenatal, non-pathological postmortem samples from 17 to 41 gestational weeks, and 3 adult controls. This dataset captures prenatal gliogenesis with high temporal resolution and is provided as a resource for further interrogation. Our computational analysis resolves greater complexity of glial progenitors, including transient glial intermediate progenitor cell (gIPC) and nascent astrocyte populations in the third trimester of human gestation. We use lineage trajectory and RNA velocity inference to further characterize specific gIPC subpopulations preceding both oligodendrocyte (gIPC-O) and astrocyte (gIPC-A) lineage differentiation. We infer unique transcriptional drivers and biological pathways associated with each developmental state, validate gIPC-A and gIPC-O presence within the human germinal matrix and cortical plate in situ, and demonstrate gIPC states being recapitulated across adult and pediatric glioblastoma tumors. Late prenatal development of the human neocortex encompasses a critical period of gliogenesis and cortical expansion. Here, authors use human transcriptomics to capture transience and diversity of cells in middle and late prenatal development, including glial progenitor signatures.
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影响因子：
25
作者：
Habib, Naomi;McCabe, Cristin;Medina, Sedi;Varshavsky, Miriam;Kitsberg, Daniel;Dvir-Szternfeld, Raz;Green, Gilad;Dionne, Danielle;Nguyen, Lan;Marshall, Jamie L.;Chen, Fei;Zhang, Feng;Kaplan, Tommy;Regev, Aviv;Schwartz, Michal
通讯作者：
Schwartz, Michal
影响因子：
17.1
作者：
Fard MK;van der Meer F;Sánchez P;Cantuti-Castelvetri L;Mandad S;Jäkel S;Fornasiero EF;Schmitt S;Ehrlich M;Starost L;Kuhlmann T;Sergiou C;Schultz V;Wrzos C;Brück W;Urlaub H;Dimou L;Stadelmann C;Simons M
通讯作者：
Simons M
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
25
作者：
Eze UC;Bhaduri A;Haeussler M;Nowakowski TJ;Kriegstein AR
通讯作者：
Kriegstein AR