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 Takasu
  • Shinya Yamanaka

Research output: Contribution to journalArticlepeer-review

5 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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