Dataset Information

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

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.

SUBMITTER: Pelletier A

PROVIDER: S-EPMC9267056 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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

Pelletier Alexandre A Carrier Arnaud A Zhao Yongmei Y Canouil Mickaël M Derhourhi Mehdi M Durand Emmanuelle E Berberian-Ferrato Lionel L Greally John J Hughes Francine F Froguel Philippe P Bonnefond Amélie A Delahaye Fabien F

International journal of molecular sciences 20220630 13

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 ...[more]

PMID: 35806330

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Project description:ObjectiveTo compare fetal heart rate (FHR) patterns during the last hour of labor between small-for-gestational-age (SGA; birth weight less than the 10th percentile for gestational age) and appropriate-for-gestational-age (AGA; birth weight at the 10-90th percentile) neonates at 36 weeks of gestation or greater. We also compared the rate of cesarean delivery and composite neonatal morbidity among SGA and AGA newborns.MethodsThis is a secondary analysis of a randomized trial of intrapartum fetal electrocardiographic ST-segment analysis. We excluded women with chorioamnionitis, insufficient duration of FHR tracing in the hour before delivery, and anomalous newborns. Fetal heart rate patterns were categorized by computerized pattern recognition software (PeriCALM Patterns). Composite neonatal morbidity was defined as any of the following: intrapartum fetal death, Apgar score 3 or less at 5 minutes, cord artery pH 7.05 or less, base deficit 12 mmol/L or greater, neonatal seizure, intubation at delivery, neonatal encephalopathy, and neonatal death. Logistic regression was used to evaluate the association between FHR patterns and SGA adjusted for magnesium sulfate exposure and stage of labor.ResultsOf the 11,108 women randomized, 85% (n=9,402) met inclusion criteria, of whom 9% were SGA. In the last hour, the likelihood of accelerations was significantly lower among SGA than AGA neonates (72.4% vs 66.8%; P=.001). Variable decelerations lasting greater than 60 seconds, with depth greater than 60 beats per minute (bpm) or nadir less than 60 bpm, were significantly more common with SGA than AGA (all P<.001). The rate of late decelerations, prolonged decelerations, or bradycardia were similar between SGA and AGA (all P>.05). Cesarean delivery for fetal indications was significantly more common with SGA (7.0%) than AGA (4.0%; P<.001). The composite neonatal morbidity was 1.4% among SGA and 1.0% among AGA (odds ratio 1.40, 95% CI 0.74-2.64).ConclusionAlthough the FHR patterns in the last hour of labor differ among SGA and AGA neonates, as does the rate of cesarean delivery, the composite neonatal morbidity was similar.

Dataset Information

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

Publications

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

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