H1FOO-DD promotes efficiency and uniformity in reprogramming to naive pluripotency.

IF 5.9 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Reports Pub Date : 2024-05-14 Epub Date: 2024-05-02 DOI:10.1016/j.stemcr.2024.04.005

Akira Kunitomi, Ryoko Hirohata, Mitsujiro Osawa, Kaho Washizu, Vanessa Arreola, Norikazu Saiki, Tomoaki M Kato, Masaki Nomura, Haruko Kunitomi, Tokiko Ohkame, Yusuke Ohkame, Jitsutaro Kawaguchi, Hiroto Hara, Kohji Kusano, Takuya Yamamoto, Yasuhiro Takashima, Shugo Tohyama, Shinsuke Yuasa, Keiichi Fukuda, Naoko Takasu, Shinya Yamanaka

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引用次数: 0

Abstract

Heterogeneity among both primed and naive pluripotent stem cell lines remains a major unresolved problem. Here we show that expressing the maternal-specific linker histone H1FOO fused to a destabilizing domain (H1FOO-DD), together with OCT4, SOX2, KLF4, and LMYC, in human somatic cells improves the quality of reprogramming to both primed and naive pluripotency. H1FOO-DD expression was associated with altered chromatin accessibility around pluripotency genes and with suppression of the innate immune response. Notably, H1FOO-DD generates naive induced pluripotent stem cells with lower variation in transcriptome and methylome among clones and a more uniform and superior differentiation potency. Furthermore, we elucidated that upregulation of FKBP1A, driven by these five factors, plays a key role in H1FOO-DD-mediated reprogramming.

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H1FOO-DD促进了向幼稚多能性重编程的效率和一致性。

原始多能干细胞系和幼稚多能干细胞系之间的异质性仍然是一个尚未解决的重大问题。在这里，我们表明，在人类体细胞中表达融合了去稳定结构域（H1FOO-DD）的母体特异性连接组蛋白H1FOO，以及OCT4、SOX2、KLF4和LMYC，可改善原始多能性和幼稚多能性的重编程质量。H1FOO-DD 的表达与多能性基因周围染色质可及性的改变以及先天性免疫反应的抑制有关。值得注意的是，H1FOO-DD产生的幼稚诱导多能干细胞的转录组和甲基组在克隆间的变异较小，分化效力更均匀、更优越。此外，我们还阐明了在这五种因子的驱动下，FKBP1A的上调在H1FOO-DD介导的重编程中发挥了关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.