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

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 TakasuShinya Yamanaka

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)710-728
Number of pages19
JournalStem Cell Reports
Volume19
Issue number5
DOIs
Publication statusPublished - 14-05-2024
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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