小柯机器人

小鼠胚胎发生过程中细胞轨迹的系统重建
2022-03-20 14:43

美国华盛顿大学Jay Shendure和Chengxiang Qiu共同合作,取得一项新突破。他们的最新研究提出了小鼠胚胎发生过程中细胞轨迹的系统重建。该研究于2022年3月14日在线发表于《自然—遗传学》杂志上。

在这里,研究人员着手整合几个单细胞RNA测序(scRNA-seq)数据集,这些数据集共同跨越小鼠原肠胚形成和器官发生,并补充了来自大约第8.5天 (E8.5) 胚胎的约 150,000 个细胞核的新分析数据。总的来说,该团队在从E3.5到E13.5的19个连续阶段中的每个阶段定义细胞状态,并启发式地将它们与它们的伪祖先和伪后代连接起来。尽管是通过自动化程序构建的,但由此产生的有向无环图(TOME(哺乳动物胚胎发生轨迹))在很大程度上与我们目前对哺乳动物发育的理解一致。该研究团队利用TOME系统地提名转录因子(TFs)作为每一种细胞类型规范的候选调节因子,以及脊椎动物进化过程中的“细胞类型同源物”。

据了解,哺乳动物胚胎发生的特点是细胞迅速增殖和多样化。在几周内,一个单细胞合子产生数百万个细胞,表达一系列的分子程序。虽然进行了深入的研究,但对构成哺乳动物体内发育的主要细胞轨迹的全面描述仍然是不清楚的。

附:英文原文

Title: Systematic reconstruction of cellular trajectories across mouse embryogenesis

Author: Qiu, Chengxiang, Cao, Junyue, Martin, Beth K., Li, Tony, Welsh, Ian C., Srivatsan, Sanjay, Huang, Xingfan, Calderon, Diego, Noble, William Stafford, Disteche, Christine M., Murray, Stephen A., Spielmann, Malte, Moens, Cecilia B., Trapnell, Cole, Shendure, Jay

Issue&Volume: 2022-03-14

Abstract: Mammalian embryogenesis is characterized by rapid cellular proliferation and diversification. Within a few weeks, a single-cell zygote gives rise to millions of cells expressing a panoply of molecular programs. Although intensively studied, a comprehensive delineation of the major cellular trajectories that comprise mammalian development in vivo remains elusive. Here, we set out to integrate several single-cell RNA-sequencing (scRNA-seq) datasets that collectively span mouse gastrulation and organogenesis, supplemented with new profiling of ~150,000 nuclei from approximately embryonic day 8.5 (E8.5) embryos staged in one-somite increments. Overall, we define cell states at each of 19 successive stages spanning E3.5 to E13.5 and heuristically connect them to their pseudoancestors and pseudodescendants. Although constructed through automated procedures, the resulting directed acyclic graph (TOME (trajectories of mammalian embryogenesis)) is largely consistent with our contemporary understanding of mammalian development. We leverage TOME to systematically nominate transcription factors (TFs) as candidate regulators of each cell type’s specification, as well as ‘cell-type homologs’ across vertebrate evolution.

DOI: 10.1038/s41588-022-01018-x

Source: https://www.nature.com/articles/s41588-022-01018-x

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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