期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 13, 页码 -出版社
MDPI
DOI: 10.3390/ijms23137323
关键词
epigenomics; single-cell; stem-cells; fetal programming; hematopoiesis
资金
- Roadmap Epigenomics Program [R01 HD063791]
- Einstein Center for Epigenomics
- Einstein Epigenomics Shared Facility
- Einstein Computational Epigenomics Group
This study reveals that excessive fetal growth leads to DNA methylation alterations and chromatin rearrangements in hematopoietic stem cells, which in turn affect the functions and quiescence signaling of these cells. This finding provides insights into the potential negative impact of fetal overgrowth on health.
Excessive fetal growth is associated with DNA methylation alterations in human hematopoietic stem and progenitor cells (HSPC), but their functional impact remains elusive. We implemented an integrative analysis combining single-cell epigenomics, single-cell transcriptomics, and in vitro analyses to functionally link DNA methylation changes to putative alterations of HSPC functions. We showed in hematopoietic stem cells (HSC) from large for gestational age neonates that both DNA hypermethylation and chromatin rearrangements target a specific network of transcription factors known to sustain stem cell quiescence. In parallel, we found a decreased expression of key genes regulating HSC differentiation including EGR1, KLF2, SOCS3, and JUNB. Our functional analyses showed that this epigenetic programming was associated with a decreased ability for HSCs to remain quiescent. Taken together, our multimodal approach using single-cell (epi)genomics showed that human fetal overgrowth affects hematopoietic stem cells' quiescence signaling via epigenetic programming.
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