幹細胞の起源(The origin of stem cells)

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2024-11-15 マックス・プランク研究所

マックス・プランク陸上微生物学研究所を含む国際研究チームは、動物の幹細胞を制御する重要なタンパク質が、動物の出現以前から存在していたことを明らかにしました。この発見は、幹細胞の進化的起源に関する新たな洞察を提供し、幹細胞の機能や再生医療への応用に影響を与える可能性があります。

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SoxとPOU転写因子の出現は、動物幹細胞の起源よりも古い The emergence of Sox and POU transcription factors predates the origins of animal stem cells

Ya Gao,Daisylyn Senna Tan,Mathias Girbig,Haoqing Hu,Xiaomin Zhou,Qianwen Xie,Shi Wing Yeung,Kin Shing Lee,Sik Yin Ho,Vlad Cojocaru,Jian Yan,Georg K. A. Hochberg,Alex de Mendoza & Ralf Jauch
Nature Communications  Published:14 November 2024
DOI:https://doi.org/10.1038/s41467-024-54152-x

幹細胞の起源(The origin of stem cells)

Abstract

Stem cells are a hallmark of animal multicellularity. Sox and POU transcription factors are associated with stemness and were believed to be animal innovations, reported absent in their unicellular relatives. Here we describe unicellular Sox and POU factors. Choanoflagellate and filasterean Sox proteins have DNA-binding specificity similar to mammalian Sox2. Choanoflagellate—but not filasterean—Sox can replace Sox2 to reprogram mouse somatic cells into induced pluripotent stem cells (iPSCs) through interacting with the mouse POU member Oct4. In contrast, choanoflagellate POU has a distinct DNA-binding profile and cannot generate iPSCs. Ancestrally reconstructed Sox proteins indicate that iPSC formation capacity is pervasive among resurrected sequences, thus loss of Sox2-like properties fostered Sox family subfunctionalization. Our findings imply that the evolution of animal stem cells might have involved the exaptation of a pre-existing set of transcription factors, where pre-animal Sox was biochemically similar to extant Sox, whilst POU factors required evolutionary innovations.

細胞遺伝子工学
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