H1FOO-DD promotes efficiency and uniformity in reprogramming to naive pluripotency
STEM CELL REPORTS(2024)
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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Key words
H1FOO,destabilized domain,Sendai virus vector,reprogramming,primed pluripotency,naive pluripotency,induced pluripotent stem cell,heterogeneity,innate immune response,FKBP1A
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