小柯机器人

中山大学贺雄雷研究小组发现，量化祖细胞的统计方法揭示细胞命运确立的萌芽阶段。2024年2月20日，国际知名学术期刊《自然—方法学》在线发表了这一成果。

研究人员提出了一种通用统计方法，通过探索记录发育过程中细胞分裂历史的细胞系统发育树，即使在缺乏祖细胞特异性标记的情况下，也能量化生物体内任何组织或细胞群的祖细胞。这种方法被称为目标聚合分析（TarCA），计算的是一个组织的两个随机取样细胞在组织特异性单系支系中聚合的概率。这个概率的倒数就是该组织的祖细胞数。

数学建模和计算机模拟都证明了TarCA的高准确性，随后研究人员又利用线虫、果蝇和小鼠的真实数据验证了TarCA的准确性，所有这些组织都有相关的细胞系统发生树。研究人员进一步证明，TarCA可用于识别胚胎发生过程中特定谱系的上调基因，并揭示了小鼠胚胎中细胞命运确立的萌芽。

研究人员表示，量化发现器官、组织或细胞群的祖细胞数量，对于了解多细胞生物体的发育和平衡至关重要。以往的工作依赖于在祖细胞中特异表达的标记基因。然而，这一策略往往因缺乏理想的标记基因而受阻。

附：英文原文

Title: A statistical method for quantifying progenitor cells reveals incipient cell fate commitments

Author: Deng, Shanjun, Gong, Han, Zhang, Di, Zhang, Mengdong, He, Xionglei

Issue&Volume: 2024-02-20

Abstract: Quantifying the number of progenitor cells that found an organ, tissue or cell population is of fundamental importance for understanding the development and homeostasis of a multicellular organism. Previous efforts rely on marker genes that are specifically expressed in progenitors. This strategy is, however, often hindered by the lack of ideal markers. Here we propose a general statistical method to quantify the progenitors of any tissues or cell populations in an organism, even in the absence of progenitor-specific markers, by exploring the cell phylogenetic tree that records the cell division history during development. The method, termed targeting coalescent analysis (TarCA), computes the probability that two randomly sampled cells of a tissue coalesce within the tissue-specific monophyletic clades. The inverse of this probability then serves as a measure of the progenitor number of the tissue. Both mathematic modeling and computer simulations demonstrated the high accuracy of TarCA, which was then validated using real data from nematode, fruit fly and mouse, all with related cell phylogenetic trees. We further showed that TarCA can be used to identify lineage-specific upregulated genes during embryogenesis, revealing incipient cell fate commitments in mouse embryos.

DOI: 10.1038/s41592-024-02189-7

Source: https://www.nature.com/articles/s41592-024-02189-7

Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex