生物
体细胞
原肠化
胚胎干细胞
斑马鱼
染色质
单细胞分析
祖细胞
细胞生物学
遗传学
干细胞
基因
细胞
作者
Sara Bizzotto,Yanmei Dou,Javier Ganz,Ryan Doan,Minseok Kwon,Craig L. Bohrson,Sonia N. Kim,Taejeong Bae,Alexej Abyzov,Peter J. Park,Christopher A. Walsh
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2021-03-19
卷期号:371 (6535): 1249-1253
被引量:59
标识
DOI:10.1126/science.abe1544
摘要
Although cell lineage information is fundamental to understanding organismal development, very little direct information is available for humans. We performed high-depth (250×) whole-genome sequencing of multiple tissues from three individuals to identify hundreds of somatic single-nucleotide variants (sSNVs). Using these variants as "endogenous barcodes" in single cells, we reconstructed early embryonic cell divisions. Targeted sequencing of clonal sSNVs in different organs (about 25,000×) and in more than 1000 cortical single cells, as well as single-nucleus RNA sequencing and single-nucleus assay for transposase-accessible chromatin sequencing of ~100,000 cortical single cells, demonstrated asymmetric contributions of early progenitors to extraembryonic tissues, distinct germ layers, and organs. Our data suggest onset of gastrulation at an effective progenitor pool of about 170 cells and about 50 to 100 founders for the forebrain. Thus, mosaic mutations provide a permanent record of human embryonic development at very high resolution.
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