Epigenetic and Transcriptomic Programming of HSC Quiescence Signaling in Large for Gestational Age Neonates

Alexandre Pelletier, Arnaud Carrier, Yongmei Zhao, Mickaël Canouil, Mehdi Derhourhi, Emmanuelle Durand, Lionel Berberian-Ferrato, John Greally, Francine Hughes, Philippe Froguel, Amélie Bonnefond, Fabien Delahaye

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number7323
JournalInternational Journal of Molecular Sciences
Volume23
Issue number13
DOIs
StatePublished - Jul 1 2022
Externally publishedYes

Keywords

  • epigenomics
  • fetal programming
  • hematopoiesis
  • single-cell
  • stem-cells

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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