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

doi:10.3390/ijms23137323

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

Genetics

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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 language	English (US)
Article number	7323
Journal	International Journal of Molecular Sciences
Volume	23
Issue number	13
DOIs	https://doi.org/10.3390/ijms23137323
State	Published - Jul 1 2022

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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10.3390/ijms23137323

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Pelletier, A., Carrier, A., Zhao, Y., Canouil, M., Derhourhi, M., Durand, E., Berberian-Ferrato, L., Greally, J., Hughes, F., Froguel, P., Bonnefond, A., & Delahaye, F. (2022). Epigenetic and Transcriptomic Programming of HSC Quiescence Signaling in Large for Gestational Age Neonates. International Journal of Molecular Sciences, 23(13), Article 7323. https://doi.org/10.3390/ijms23137323

Pelletier, A, Carrier, A, Zhao, Y, Canouil, M, Derhourhi, M, Durand, E, Berberian-Ferrato, L, Greally, J, Hughes, F, Froguel, P, Bonnefond, A & Delahaye, F 2022, 'Epigenetic and Transcriptomic Programming of HSC Quiescence Signaling in Large for Gestational Age Neonates', International Journal of Molecular Sciences, vol. 23, no. 13, 7323. https://doi.org/10.3390/ijms23137323

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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{\textquoteright} quiescence signaling via epigenetic programming.",

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AU - Derhourhi, Mehdi

AU - Durand, Emmanuelle

AU - Berberian-Ferrato, Lionel

AU - Greally, John

AU - Hughes, Francine

AU - Froguel, Philippe

AU - Bonnefond, Amélie

AU - Delahaye, Fabien

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

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