小柯机器人

英国威康桑格研究所Sarah A. Teichmann等研究人员合作绘制出空间和时间分辨率的人类胚胎肢体细胞图谱。2023年12月6日，《自然》杂志在线发表了这项成果。

研究人员利用单细胞和空间转录组学详细描述了人类胚胎肢体在不同时间和空间的发育过程。研究人员展示了细胞从少数多能祖细胞到无数分化细胞状态的广泛多样化，其中包括几种新型细胞群。研究人员发现了人类肌肉发育的两个阶段，每个阶段的特征都是由不同基因表达程序调控的不同细胞状态，并确定肌肉蛋白（MSC）是维持肌肉干细胞特征的关键转录抑制因子。

通过使用VisiumStitcher组装多个解剖学上连续的空间转录组样本，研究人员绘制了整个胎儿后肢矢状切面的细胞图谱。研究人员揭示了与手足畸形和多指畸形相关的基因之间明显的解剖学分离，并发现了自足间充质在转录和空间上的不同群体。最后，研究人员对小鼠胚胎肢体进行了单细胞RNA测序，以便进行跨物种发育比较，结果发现两个物种之间存在大量同源性。

据悉，人的四肢在受孕后第四周以间质芽的形式出现，并在随后的几个月中发育成完全成型的四肢。这一过程由许多受时间和空间限制的基因表达程序控制，因此先天性表型改变很常见。数十年来对模型生物的研究已经确定了脊椎动物肢体发育的基本机制，但对人类肢体发育过程的深入研究仍有待进行。

附：英文原文

Title: A human embryonic limb cell atlas resolved in space and time

Author: Zhang, Bao, He, Peng, Lawrence, John E. G., Wang, Shuaiyu, Tuck, Elizabeth, Williams, Brian A., Roberts, Kenny, Kleshchevnikov, Vitalii, Mamanova, Lira, Bolt, Liam, Polanski, Krzysztof, Li, Tong, Elmentaite, Rasa, Fasouli, Eirini S., Prete, Martin, He, Xiaoling, Yayon, Nadav, Fu, Yixi, Yang, Hao, Liang, Chen, Zhang, Hui, Blain, Raphael, Chedotal, Alain, FitzPatrick, David R., Firth, Helen, Dean, Andrew, Bayraktar, Omer Ali, Marioni, John C., Barker, Roger A., Storer, Mekayla A., Wold, Barbara J., Zhang, Hongbo, Teichmann, Sarah A.

Issue&Volume: 2023-12-06

Abstract: Human limbs emerge during the fourth post-conception week as mesenchymal buds, which develop into fully formed limbs over the subsequent months1. This process is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common2. Decades of work with model organisms have defined the fundamental mechanisms underlying vertebrate limb development, but an in-depth characterization of this process in humans has yet to be performed. Here we detail human embryonic limb development across space and time using single-cell and spatial transcriptomics. We demonstrate extensive diversification of cells from a few multipotent progenitors to myriad differentiated cell states, including several novel cell populations. We uncover two waves of human muscle development, each characterized by different cell states regulated by separate gene expression programmes, and identify musculin (MSC) as a key transcriptional repressor maintaining muscle stem cell identity. Through assembly of multiple anatomically continuous spatial transcriptomic samples using VisiumStitcher, we map cells across a sagittal section of a whole fetal hindlimb. We reveal a clear anatomical segregation between genes linked to brachydactyly and polysyndactyly, and uncover transcriptionally and spatially distinct populations of the mesenchyme in the autopod. Finally, we perform single-cell RNA sequencing on mouse embryonic limbs to facilitate cross-species developmental comparison, finding substantial homology between the two species.

DOI: 10.1038/s41586-023-06806-x

Source: https://www.nature.com/articles/s41586-023-06806-x

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