Epigenetic and Transcriptomic Programming of HSC Quiescence Signaling in Large for Gestational Age Neonates
Year: 2022
Type: article
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.
DOI: 10.3390/ijms23137323
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,206
Funders: Equipex, European Genomic Institute for Diabetes, European Commission, Agence Nationale de la Recherche, Conseil Régional Hauts-de-France, National Institutes of Health, Medical Research Council, European Regional Development Fund, National Institute on Aging, Eunice Kennedy Shriver National Institute of Child Health and Human Development, H2020 European Research Council, CHIST-ERA
Awards: PreciDIAB Institute, the holistic approach of personal diabets care, G195474297, G2178648417, G3479052434, G3533229685, G3976661348, EGID Diabetes Pole, G4656594441, G4815328311, UNDERSTANDING CELLULAR AND TRANSCRIPTIONAL REGULATORY CHANGES IN HUMAN AGING, Targeting GLP-1 receptor trafficking to improve therapies for type 2 diabetes, G6865802051, G7010305552, Functional genomics of non-coding mutations in regulatory regions of four metabolic tissues, and their involvement into type 2 diabetes through large-scale sequencing, Plate forme Lilloise de séquençage du génome humain pour une médecine personnalisée, G7240651115, G8088323586, G8510727784, Genome-wide DNA Methylation Profiles Associated with Abnormal Intrauterine Growth, SUPPORT FOR THE ROSE F KENNEDY IDDRC P50
OpenAlex ID: W4283737792