美国加州大学Karen Oegema等研究人员实现胚胎发育过程中基因功能的自动剖析。这一研究成果于2024年5月16日在线发表在国际学术期刊《细胞》上。

研究人员表示，对指导胚胎发育的基因组进行系统功能分析是一项重要挑战。

为了应对这一挑战，研究人员利用秀丽隐杆线虫胚胎发生的4D成像捕捉了500个基因敲除的影响，并开发了一种自动方法来比较发育表型。该自动方法量化了包括生殖层细胞数量、组织位置和组织形状在内的特征，生成了时间曲线，其参数化产生了数字表型特征。这些特征与跨表型空间的新相似度量相结合，生成了预测具有相似功能的基因排序列表，可在PhenoBank门户网站上访问25%的重要发育基因。

这种方法确定了细胞命运特化和形态发生中新的基因和通路关系，并强调了胚胎发生过程中特殊能量生成通路的利用。

总之，这项工作为全面分析构建多细胞生物体的基因集奠定了基础。

附：英文原文

Title: Automated profiling of gene function during embryonic development

Author: Rebecca A. Green, Renat N. Khaliullin, Zhiling Zhao, Stacy D. Ochoa, Jeffrey M. Hendel, Tiffany-Lynn Chow, HongKee Moon, Ronald J. Biggs, Arshad Desai, Karen Oegema

Issue&Volume: 2024-05-16

Abstract: Systematic functional profiling of the gene set that directs embryonic developmentis an important challenge. To tackle this challenge, we used 4D imaging of C. elegans embryogenesis to capture the effects of 500 gene knockdowns and developed an automatedapproach to compare developmental phenotypes. The automated approach quantifies features—includinggerm layer cell numbers, tissue position, and tissue shape—to generate temporal curveswhose parameterization yields numerical phenotypic signatures. In conjunction witha new similarity metric that operates across phenotypic space, these signatures enabledthe generation of ranked lists of genes predicted to have similar functions, accessiblein the PhenoBank web portal, for ～25% of essential development genes. The approachidentified new gene and pathway relationships in cell fate specification and morphogenesisand highlighted the utilization of specialized energy generation pathways during embryogenesis.Collectively, the effort establishes the foundation for comprehensive analysis of the gene set that builds a multicellular organism.

DOI: 10.1016/j.cell.2024.04.012

Source: https://www.cell.com/cell/abstract/S0092-8674(24)00407-0