Epigenetic and Transcriptomic Programming of HSC Quiescence Signaling in Large for Gestational Age Neonates.
Alexandre PelletierArnaud CarrierYongmei ZhaoMickaël CanouilMehdi DerhourhiEmmanuelle DurandLionel Berberian-FerratoJohn GreallyFrancine HughesPhilippe FroguelAmélie BonnefondFabien DelahayePublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- single cell
- dna methylation
- stem cells
- gestational age
- genome wide
- rna seq
- gene expression
- birth weight
- preterm birth
- transcription factor
- endothelial cells
- high throughput
- low birth weight
- induced pluripotent stem cells
- cell therapy
- weight gain
- pluripotent stem cells
- poor prognosis
- copy number
- circulating tumor
- long non coding rna
- binding protein
- preterm infants
- oxidative stress
- mesenchymal stem cells