Developmental landscape of human forebrain at a single-cell level identifies early waves of oligodendrogenesis

被引:32
作者
van Bruggen, David [1 ]
Pohl, Fabio [1 ]
Langseth, Christoffer Mattsson [2 ]
Kukanja, Petra [1 ]
Lee, Hower [2 ]
Albiach, Alejandro Mossi [1 ]
Kabbe, Mukund [1 ]
Meijer, Mandy [1 ]
Linnarsson, Sten [1 ]
Hilscher, Markus M. [2 ]
Nilsson, Mats [2 ]
Sundstrom, Erik [3 ]
Castelo-Branco, Goncalo [1 ,4 ]
机构
[1] Karolinska Inst, Lab Mol Neurobiol, Dept Med Biochem & Biophys, Biomed, S-17177 Stockholm, Sweden
[2] Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, S-17165 Solna, Sweden
[3] Karolinska Inst, BioClinicum, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Solna, Sweden
[4] Karolinska Inst, Ming Wai Lau Ctr Reparat Med, Stockholm Node, Stockholm, Sweden
基金
瑞典研究理事会; 欧盟地平线“2020”;
关键词
NEURAL STEM-CELLS; RADIAL GLIA; NOTCH; OLIGODENDROCYTES; SPECIFICATION; REQUIREMENT; EXPRESSION; DIFFERENTIATION; ACCESSIBILITY; GENES;
D O I
10.1016/j.devcel.2022.04.016
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Oligodendrogenesis in the human central nervous system has been observed mainly at the second trimester of gestation, a much later developmental stage compared to oligodendrogenesis in mice. Here, we characterize the transcriptomic neural diversity in the human forebrain at post-conception weeks (PCW) 8???10. Using single-cell RNA sequencing, we find evidence of the emergence of a first wave of oligodendrocyte lineage cells as early as PCW 8, which we also confirm at the epigenomic level through the use of single-cell ATAC-seq. Using regulatory network inference, we predict key transcriptional events leading to the specification of oligodendrocyte precursor cells (OPCs). Moreover, by profiling the spatial expression of 50 key genes through the use of in situ sequencing (ISS), we identify regions in the human ventral fetal forebrain where oligodendrogenesis first occurs. Our results indicate evolutionary conservation of the first wave of oligodendrogenesis between mice and humans and describe regulatory mechanisms involved in human OPC specification.
引用
收藏
页码:1421 / +
页数:22
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