TY - JOUR
T1 - Epigenetic and Transcriptomic Programming of HSC Quiescence Signaling in Large for Gestational Age Neonates
AU - Pelletier, Alexandre
AU - Carrier, Arnaud
AU - Zhao, Yongmei
AU - Canouil, Mickaël
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
N1 - Funding Information:
Acknowledgments: The authors thank the UMR 8199 LIGAN-PM Genomics platform (Lille, France) which belongs to the ‘Federation de Recherche’ 3508 Labex EGID (European Genomics Institute for Diabetes; ANR-10-LABX-46) and was supported by the ANR Equipex 2010 session (ANR-10-EQPX-07-01; ‘LIGAN-PM’). The LIGAN-PM Genomics platform (Lille, France) is also supported by the FEDER and the Region Nord-Pas-de-Calais-Picardie. This project is cofunded in the frame of CPER CTRL program by the European Union—European Regional Development Fund (ERDF), Hauts de France Region (contract n°17003781), Métropole Européenne de Lille (contract n°2016_ESR_05), and French State (contract n°2017-R3-CTRL-Phase 1). The present work was also supported by the National Center for Precision Diabetic Medicine—PreciDIAB, which is jointly supported by the French National Agency for Research (ANR-18-IBHU-0001), by the European Union (FEDER), by the Hauts-de-France Regional Council and by the European Metropolis of Lille (MEL) and by the European Research Council (ERC Reg-Seq—715575). We thank “France Génomique” consortium (ANR-10-INBS-009).
Funding Information:
Support for this project was provided by the Roadmap Epigenomics Program, R01 HD063791 (Einstein/Greally). Support was also provided by Einstein’s Center for Epigenomics, including the Epigenomics Shared Facility and Computational Epigenomics Group.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - 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.
AB - 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.
KW - epigenomics
KW - fetal programming
KW - hematopoiesis
KW - single-cell
KW - stem-cells
UR - http://www.scopus.com/inward/record.url?scp=85133124211&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85133124211&partnerID=8YFLogxK
U2 - 10.3390/ijms23137323
DO - 10.3390/ijms23137323
M3 - Article
AN - SCOPUS:85133124211
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 13
M1 - 7323
ER -