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H1FOO-DD promotes efficiency and uniformity in reprogramming to naive pluripotency
Akira Kunitomi1, Ryoko Hirohata2, Mitsujiro Osawa3
1Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan; Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
Stem Cell Reports
|May 3, 2024
Summary
Introducing H1FOO-DD, a novel factor, significantly enhances the quality of induced pluripotent stem cells (iPSCs). This breakthrough improves reprogramming efficiency and reduces cellular variation, paving the way for more uniform and potent stem cell therapies.
Area of Science:
- Stem cell biology
- Epigenetics
- Cellular reprogramming
Background:
- Heterogeneity in primed and naive pluripotent stem cell lines is a significant challenge.
- Improving the quality and uniformity of induced pluripotent stem cells (iPSCs) is crucial for therapeutic applications.
Purpose of the Study:
- To investigate the role of the maternal-specific linker histone H1FOO fused to a destabilizing domain (H1FOO-DD) in improving stem cell reprogramming.
- To characterize the effects of H1FOO-DD on chromatin accessibility, immune response, and the quality of naive iPSCs.
Main Methods:
- Expression of H1FOO-DD with reprogramming factors (OCT4, SOX2, KLF4, LMYC) in human somatic cells.
- Analysis of chromatin accessibility, transcriptome, and methylome variations in generated iPSCs.
- Assessment of differentiation potency and identification of key molecular players in the reprogramming process.
Main Results:
- H1FOO-DD expression improved reprogramming to both primed and naive pluripotency.
- H1FOO-DD altered chromatin accessibility near pluripotency genes and suppressed innate immune responses.
- Naive iPSCs generated with H1FOO-DD exhibited reduced transcriptome and methylome heterogeneity and superior differentiation potential.
- Upregulation of FKBP1A was identified as a key factor in H1FOO-DD-mediated reprogramming.
Conclusions:
- H1FOO-DD enhances the quality and uniformity of induced pluripotent stem cells, addressing a major challenge in the field.
- The mechanism involves epigenetic modifications, immune response modulation, and upregulation of FKBP1A.
- This finding offers a promising strategy for generating more reliable and potent iPSCs for regenerative medicine.
Keywords:
FKBP1AH1FOOSendai virus vectordestabilized domainheterogeneityinduced pluripotent stem cellinnate immune responsenaive pluripotencyprimed pluripotencyreprogrammingMore Related Videos
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