小柯机器人

人与黑猩猩的融合细胞揭示了骨骼进化过程中的顺式调控差异，这一成果美国由斯坦福大学Hunter B. Fraser、David Gokhman研究小组经过不懈努力而取得。相关论文于2021年3月17日发表在《自然-遗传学》杂志上。

研究人员利用人与黑猩猩杂交诱导的多能干细胞来研究造成物种分离的基因表达。四倍体杂交细胞使研究人员能够将顺式与反式调节作用分开，并控制非遗传混杂因素。研究人员将这些细胞分化为颅神经c细胞，这是面部构成的主要细胞类型。

研究人员发现hedgehog信号通路的谱系特异性选择证据，其中包括人关键hedgehog基因EVC2（LIMBIN）的下调，其下调幅度达六倍。诱导EVC2的下调大大降低了hedgehog信号的输出。缺乏功能性EVC2的小鼠和人类表现出相似的表型，这与人-黑猩猩融合颅面差异相似，这表明hedgehog信号的调节差异可能是人独特颅面形态的原因。

据介绍，基因调控差异被认为在人类特异性特征产生过程中起着核心作用。但是，将不同的调控与不同表型联系起来的能力是有限的。

附：英文原文

Title: Human–chimpanzee fused cells reveal cis -regulatory divergence underlying skeletal evolution

Author: David Gokhman, Rachel M. Agoglia, Maia Kinnebrew, Wei Gordon, Danqiong Sun, Vivek K. Bajpai, Sahin Naqvi, Coral Chen, Anthony Chan, Chider Chen, Dmitri A. Petrov, Nadav Ahituv, Honghao Zhang, Yuji Mishina, Joanna Wysocka, Rajat Rohatgi, Hunter B. Fraser

Issue&Volume: 2021-03-17

Abstract: Gene regulatory divergence is thought to play a central role in determining human-specific traits. However, our ability to link divergent regulation to divergent phenotypes is limited. Here, we utilized human–chimpanzee hybrid induced pluripotent stem cells to study gene expression separating these species. The tetraploid hybrid cells allowed us to separate cis- from trans-regulatory effects, and to control for nongenetic confounding factors. We differentiated these cells into cranial neural crest cells, the primary cell type giving rise to the face. We discovered evidence of lineage-specific selection on the hedgehog signaling pathway, including a human-specific sixfold down-regulation of EVC2 (LIMBIN), a key hedgehog gene. Inducing a similar down-regulation of EVC2 substantially reduced hedgehog signaling output. Mice and humans lacking functional EVC2 show striking phenotypic parallels to human–chimpanzee craniofacial differences, suggesting that the regulatory divergence of hedgehog signaling may have contributed to the unique craniofacial morphology of humans.

DOI: 10.1038/s41588-021-00804-3

Source: https://www.nature.com/articles/s41588-021-00804-3

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