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Updated: Sep 5, 2025

Reprogramming Mouse Embryonic Fibroblasts with Transcription Factors to Induce a Hemogenic Program
Published on: December 16, 2016
Epigenetic and Transcriptomic Programming of HSC Quiescence Signaling in Large for Gestational Age Neonates
Alexandre Pelletier1,2, Arnaud Carrier1,2, Yongmei Zhao3
1Inserm U1283, CNRS UMR 8199, European Genomic Institute for Diabetes, Institut Pasteur de Lille, 59000 Lille, France.
Abstract:
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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