韩国科学技术院Young Seok Ju、庆北大学Ji Won Oh等研究人员合作揭示人类早期胚胎发育的克隆动态。相关论文于2021年8月25日在线发表在《自然》杂志上。
研究人员探索了334个单细胞克隆的全基因组，以及从7个最近去世成年人类捐赠者不同解剖位置获得的379个大块组织的定向深层序列。使用体细胞突变作为内在的条形码，研究人员重建了早期细胞的系统发育，并表明：（1）内源性突变率在第一次细胞分裂时较高，但在以后的每个细胞分裂中下降到大约一个；（2）早期细胞对胚胎本身的贡献普遍不平等，这是由于早期细胞瓶颈随机地将胚胎内的外胚层细胞搁置；（3）身体左右两侧组织、不同胚层和特定解剖部位和器官之间不同程度的早期克隆不平衡；（4）少数祖先细胞的出现，这些细胞能够大大促进血液和肝脏的成人细胞库；以及（5）受精卵中存在线粒体DNA异质性。这个方法还提供了对与年龄有关的突变过程和正常体细胞中性染色体丢失的深入了解。
总之，这项研究为今后的研究提供了基础，可用于完成人类胚胎发育中的细胞系统发育。
据悉，由于在人类胚胎中研究具有难度，人类早期胚胎发育的细胞动力学和命运决定在很大程度上仍然是未知的。
附：英文原文
Title: Clonal dynamics in early human embryogenesis inferred from somatic mutation
Author: Park, Seongyeol, Mali, Nanda Maya, Kim, Ryul, Choi, Jeong-Woo, Lee, Junehawk, Lim, Joonoh, Park, Jung Min, Park, Jung Woo, Kim, Donghyun, Kim, Taewoo, Yi, Kijong, Choi, June Hyug, Kwon, Seong Gyu, Hong, Joo Hee, Youk, Jeonghwan, An, Yohan, Kim, Su Yeon, Oh, Soo A, Kwon, Youngoh, Hong, Dongwan, Kim, Moonkyu, Kim, Dong Sun, Park, Ji Young, Oh, Ji Won, Ju, Young Seok
Issue&Volume: 2021-08-25
Abstract: Cellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos1. Here, we explored whole-genomes of 334 single-cell colonies and targeted deep sequences of 379 bulk tissues obtained from various anatomical locations of seven recently deceased adult human donors. Using somatic mutations as an intrinsic barcode, we reconstructed early cellular phylogenies that demonstrate (1) an endogenous mutational rate that is higher in the first cell division but decreases to approximately one per cell per cell division later in life; (2) universal unequal contribution of early cells to embryo proper, resulting from early cellular bottlenecks that stochastically set aside epiblast cells within the embryo; (3) examples of varying degrees of early clonal imbalances between tissues on the left and right sides of the body, different germ layers and specific anatomical parts and organs; (4) emergence of a few ancestral cells that will substantially contribute to adult cell pools in blood and liver; and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach also provides insights into the age-related mutational processes and loss of sex chromosomes in normal somatic cells. In sum, this study provides a foundation for future studies to complete cellular phylogenies in human embryogenesis. Adult human tissues from diverse sites around the body are used to reconstruct cellular phylogenies from early development, using somatic mutations as an internal barcode.
DOI: 10.1038/s41586-021-03786-8
Source: https://www.nature.com/articles/s41586-021-03786-8
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
