Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia

Autores
Cho, Hye-Youn; Wang, Xuting; Campbell, Michelle R.; Panduri, Vijayalakshmi; Coviello, Silvina Andrea; Caballero, Mauricio Tomás; Bennett, Brian D.; Kleeberger, Steven R.; Polack, Fernando Pedro; Ofman, Gaston; Bell, Douglas A.
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Bronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease of prematurity with limited treatment options. To uncover biomarkers of BPD risk, this study investigated epigenetic and transcriptomic signatures of prematurity at birth and during the neonatal period at day 14 and 28. Peripheral blood DNAs from preterm infants were applied to methylation arrays and cell-type composition was estimated by deconvolution. Covariate-adjusted robust linear regression elucidated BPD- and prolonged oxygen (≥ 14 days) exposure-associated CpGs. RNAs from cord and peripheral blood were sequenced, and differentially expressed genes (DEGs) for BPD or oxygen exposure were determined. Estimated neutrophil–lymphocyte ratios in peripheral blood at day 14 in BPD infants were significantly higher than nonBPD infants, suggesting an heightened inflammatory response in developing BPD. BPD-DEGs in cord blood indicated lymphopoiesis inhibition, altered Th1/Th2 responses, DNA damage, and organ degeneration. On day 14, BPD-associated CpGs were highly enriched in neutrophil activation, infection, and CD4 + T cell quantity, and BPD-DEGs were involved in DNA damage, cellular senescence, T cell homeostasis, and hyper-cytokinesis. On day 28, BPD-associated CpGs along with BPD-DEGs were enriched for phagocytosis, neurological disorder, and nucleotide metabolism. Oxygen supplementation markedly downregulated mitochondrial biogenesis genes and altered CpGs annotated to developmental genes. Prematurity-altered DNA methylation could cause abnormal lymphopoiesis, cellular assembly and cell cycle progression to increase BPD risk. Similar pathways between epigenome and transcriptome networks suggest coordination of the two in dysregulating leukopoiesis, adaptive immunity, and innate immunity. The results provide molecular insights into biomarkers for early detection and prevention of BPD.
Fil: Cho, Hye-Youn. National Institutes of Health; Estados Unidos
Fil: Wang, Xuting. National Institutes of Health; Estados Unidos
Fil: Campbell, Michelle R.. National Institutes of Health; Estados Unidos
Fil: Panduri, Vijayalakshmi. National Institutes of Health; Estados Unidos
Fil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Bennett, Brian D.. National Institutes of Health; Estados Unidos
Fil: Kleeberger, Steven R.. National Institutes of Health; Estados Unidos
Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos
Fil: Ofman, Gaston. Fundación para la Investigación en Infectología Infantil; Argentina. University of Oklahoma Health Sciences Center; Estados Unidos
Fil: Bell, Douglas A.. National Institutes of Health; Estados Unidos
Materia
Displasia broncopulmonar
Inmunidad
Biomarcadores
Epigenoma
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/220827
Acceder
id CONICETDig_55da36f171e5b11934d3e31ce509fdb5
oai_identifier_str oai:ri.conicet.gov.ar:11336/220827
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasiaCho, Hye-YounWang, XutingCampbell, Michelle R.Panduri, VijayalakshmiCoviello, Silvina AndreaCaballero, Mauricio TomásBennett, Brian D.Kleeberger, Steven R.Polack, Fernando PedroOfman, GastonBell, Douglas A.Displasia broncopulmonarInmunidadBiomarcadoresEpigenomahttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Bronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease of prematurity with limited treatment options. To uncover biomarkers of BPD risk, this study investigated epigenetic and transcriptomic signatures of prematurity at birth and during the neonatal period at day 14 and 28. Peripheral blood DNAs from preterm infants were applied to methylation arrays and cell-type composition was estimated by deconvolution. Covariate-adjusted robust linear regression elucidated BPD- and prolonged oxygen (≥ 14 days) exposure-associated CpGs. RNAs from cord and peripheral blood were sequenced, and differentially expressed genes (DEGs) for BPD or oxygen exposure were determined. Estimated neutrophil–lymphocyte ratios in peripheral blood at day 14 in BPD infants were significantly higher than nonBPD infants, suggesting an heightened inflammatory response in developing BPD. BPD-DEGs in cord blood indicated lymphopoiesis inhibition, altered Th1/Th2 responses, DNA damage, and organ degeneration. On day 14, BPD-associated CpGs were highly enriched in neutrophil activation, infection, and CD4 + T cell quantity, and BPD-DEGs were involved in DNA damage, cellular senescence, T cell homeostasis, and hyper-cytokinesis. On day 28, BPD-associated CpGs along with BPD-DEGs were enriched for phagocytosis, neurological disorder, and nucleotide metabolism. Oxygen supplementation markedly downregulated mitochondrial biogenesis genes and altered CpGs annotated to developmental genes. Prematurity-altered DNA methylation could cause abnormal lymphopoiesis, cellular assembly and cell cycle progression to increase BPD risk. Similar pathways between epigenome and transcriptome networks suggest coordination of the two in dysregulating leukopoiesis, adaptive immunity, and innate immunity. The results provide molecular insights into biomarkers for early detection and prevention of BPD.Fil: Cho, Hye-Youn. National Institutes of Health; Estados UnidosFil: Wang, Xuting. National Institutes of Health; Estados UnidosFil: Campbell, Michelle R.. National Institutes of Health; Estados UnidosFil: Panduri, Vijayalakshmi. National Institutes of Health; Estados UnidosFil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bennett, Brian D.. National Institutes of Health; Estados UnidosFil: Kleeberger, Steven R.. National Institutes of Health; Estados UnidosFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados UnidosFil: Ofman, Gaston. Fundación para la Investigación en Infectología Infantil; Argentina. University of Oklahoma Health Sciences Center; Estados UnidosFil: Bell, Douglas A.. National Institutes of Health; Estados UnidosNature Research2023-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/220827Cho, Hye-Youn; Wang, Xuting; Campbell, Michelle R.; Panduri, Vijayalakshmi; Coviello, Silvina Andrea; et al.; Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia; Nature Research; Scientific Reports; 13; 1; 7-2023; 1-212045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-023-39313-0info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-023-39313-0info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:32:33Zoai:ri.conicet.gov.ar:11336/220827instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:32:33.318CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia
title Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia
spellingShingle Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia
Cho, Hye-Youn
Displasia broncopulmonar
Inmunidad
Biomarcadores
Epigenoma
title_short Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia
title_full Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia
title_fullStr Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia
title_full_unstemmed Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia
title_sort Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia
dc.creator.none.fl_str_mv Cho, Hye-Youn
Wang, Xuting
Campbell, Michelle R.
Panduri, Vijayalakshmi
Coviello, Silvina Andrea
Caballero, Mauricio Tomás
Bennett, Brian D.
Kleeberger, Steven R.
Polack, Fernando Pedro
Ofman, Gaston
Bell, Douglas A.
author Cho, Hye-Youn
author_facet Cho, Hye-Youn
Wang, Xuting
Campbell, Michelle R.
Panduri, Vijayalakshmi
Coviello, Silvina Andrea
Caballero, Mauricio Tomás
Bennett, Brian D.
Kleeberger, Steven R.
Polack, Fernando Pedro
Ofman, Gaston
Bell, Douglas A.
author_role author
author2 Wang, Xuting
Campbell, Michelle R.
Panduri, Vijayalakshmi
Coviello, Silvina Andrea
Caballero, Mauricio Tomás
Bennett, Brian D.
Kleeberger, Steven R.
Polack, Fernando Pedro
Ofman, Gaston
Bell, Douglas A.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Displasia broncopulmonar
Inmunidad
Biomarcadores
Epigenoma
topic Displasia broncopulmonar
Inmunidad
Biomarcadores
Epigenoma
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Bronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease of prematurity with limited treatment options. To uncover biomarkers of BPD risk, this study investigated epigenetic and transcriptomic signatures of prematurity at birth and during the neonatal period at day 14 and 28. Peripheral blood DNAs from preterm infants were applied to methylation arrays and cell-type composition was estimated by deconvolution. Covariate-adjusted robust linear regression elucidated BPD- and prolonged oxygen (≥ 14 days) exposure-associated CpGs. RNAs from cord and peripheral blood were sequenced, and differentially expressed genes (DEGs) for BPD or oxygen exposure were determined. Estimated neutrophil–lymphocyte ratios in peripheral blood at day 14 in BPD infants were significantly higher than nonBPD infants, suggesting an heightened inflammatory response in developing BPD. BPD-DEGs in cord blood indicated lymphopoiesis inhibition, altered Th1/Th2 responses, DNA damage, and organ degeneration. On day 14, BPD-associated CpGs were highly enriched in neutrophil activation, infection, and CD4 + T cell quantity, and BPD-DEGs were involved in DNA damage, cellular senescence, T cell homeostasis, and hyper-cytokinesis. On day 28, BPD-associated CpGs along with BPD-DEGs were enriched for phagocytosis, neurological disorder, and nucleotide metabolism. Oxygen supplementation markedly downregulated mitochondrial biogenesis genes and altered CpGs annotated to developmental genes. Prematurity-altered DNA methylation could cause abnormal lymphopoiesis, cellular assembly and cell cycle progression to increase BPD risk. Similar pathways between epigenome and transcriptome networks suggest coordination of the two in dysregulating leukopoiesis, adaptive immunity, and innate immunity. The results provide molecular insights into biomarkers for early detection and prevention of BPD.
Fil: Cho, Hye-Youn. National Institutes of Health; Estados Unidos
Fil: Wang, Xuting. National Institutes of Health; Estados Unidos
Fil: Campbell, Michelle R.. National Institutes of Health; Estados Unidos
Fil: Panduri, Vijayalakshmi. National Institutes of Health; Estados Unidos
Fil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Caballero, Mauricio Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Bennett, Brian D.. National Institutes of Health; Estados Unidos
Fil: Kleeberger, Steven R.. National Institutes of Health; Estados Unidos
Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos
Fil: Ofman, Gaston. Fundación para la Investigación en Infectología Infantil; Argentina. University of Oklahoma Health Sciences Center; Estados Unidos
Fil: Bell, Douglas A.. National Institutes of Health; Estados Unidos
description Bronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease of prematurity with limited treatment options. To uncover biomarkers of BPD risk, this study investigated epigenetic and transcriptomic signatures of prematurity at birth and during the neonatal period at day 14 and 28. Peripheral blood DNAs from preterm infants were applied to methylation arrays and cell-type composition was estimated by deconvolution. Covariate-adjusted robust linear regression elucidated BPD- and prolonged oxygen (≥ 14 days) exposure-associated CpGs. RNAs from cord and peripheral blood were sequenced, and differentially expressed genes (DEGs) for BPD or oxygen exposure were determined. Estimated neutrophil–lymphocyte ratios in peripheral blood at day 14 in BPD infants were significantly higher than nonBPD infants, suggesting an heightened inflammatory response in developing BPD. BPD-DEGs in cord blood indicated lymphopoiesis inhibition, altered Th1/Th2 responses, DNA damage, and organ degeneration. On day 14, BPD-associated CpGs were highly enriched in neutrophil activation, infection, and CD4 + T cell quantity, and BPD-DEGs were involved in DNA damage, cellular senescence, T cell homeostasis, and hyper-cytokinesis. On day 28, BPD-associated CpGs along with BPD-DEGs were enriched for phagocytosis, neurological disorder, and nucleotide metabolism. Oxygen supplementation markedly downregulated mitochondrial biogenesis genes and altered CpGs annotated to developmental genes. Prematurity-altered DNA methylation could cause abnormal lymphopoiesis, cellular assembly and cell cycle progression to increase BPD risk. Similar pathways between epigenome and transcriptome networks suggest coordination of the two in dysregulating leukopoiesis, adaptive immunity, and innate immunity. The results provide molecular insights into biomarkers for early detection and prevention of BPD.
publishDate 2023
dc.date.none.fl_str_mv 2023-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/220827
Cho, Hye-Youn; Wang, Xuting; Campbell, Michelle R.; Panduri, Vijayalakshmi; Coviello, Silvina Andrea; et al.; Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia; Nature Research; Scientific Reports; 13; 1; 7-2023; 1-21
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/220827
identifier_str_mv Cho, Hye-Youn; Wang, Xuting; Campbell, Michelle R.; Panduri, Vijayalakshmi; Coviello, Silvina Andrea; et al.; Prospective epigenome and transcriptome analyses of cord and peripheral blood from preterm infants at risk of bronchopulmonary dysplasia; Nature Research; Scientific Reports; 13; 1; 7-2023; 1-21
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-023-39313-0
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-023-39313-0
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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