Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth

Noboru J. Sakabe; Ivy Aneas; Nicholas Knoblauch; Debora R. Sobreira; Nicole Clark; Cristina Paz; Cynthia Horth; Ryan Ziffra; Harjot Kaur; Xiao Liu; Rebecca Anderson; Jean Morrison; Virginia C. Cheung; Chad Grotegut; Timothy E. Reddy; Bo Jacobsson; Mikko Hallman; Kari Teramo; Amy Murtha; John Kessler; William Grobman; Ge Zhang; Louis J. Muglia; Sarosh Rana; Vincent J. Lynch; Gregory E. Crawford; Carole Ober; Xin He; Marcelo A. Nóbrega

doi:10.1126/sciadv.abc8696

Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth

Noboru J. Sakabe, Ivy Aneas, Nicholas Knoblauch, Debora R. Sobreira, Nicole Clark, Cristina Paz, Cynthia Horth, Ryan Ziffra, Harjot Kaur, Xiao Liu, Rebecca Anderson, Jean Morrison, Virginia C. Cheung, Chad Grotegut, Timothy E. Reddy, Bo Jacobsson, Mikko Hallman, Kari Teramo, Amy Murtha, John KesslerWilliam Grobman, Ge Zhang, Louis J. Muglia, Sarosh Rana, Vincent J. Lynch, Gregory E. Crawford, Carole Ober^*, Xin He^*, Marcelo A. Nóbrega^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

While a genetic component of preterm birth (PTB) has long been recognized and recently mapped by genome-wide association studies (GWASs), the molecular determinants underlying PTB remain elusive. This stems in part from an incomplete availability of functional genomic annotations in human cell types relevant to pregnancy and PTB. We generated transcriptome (RNA-seq), epigenome (ChIP-seq of H3K27ac, H3K4me1, and H3K4me3 histone modifications), open chromatin (ATAC-seq), and chromatin interaction (promoter capture Hi-C) annotations of cultured primary decidua-derived mesenchymal stromal/stem cells and in vitro differentiated decidual stromal cells and developed a computational framework to integrate these functional annotations with results from a GWAS of gestational duration in 56,384 women. Using these resources, we uncovered additional loci associated with gestational duration and target genes of associated loci. Our strategy illustrates how functional annotations in pregnancy-relevant cell types aid in the experimental follow-up of GWAS for PTB and, likely, other pregnancy-related conditions.

Original language	English (US)
Article number	eabc8696
Journal	Science Advances
Volume	6
Issue number	49
DOIs	https://doi.org/10.1126/sciadv.abc8696
State	Published - Dec 2 2020

Funding

We acknowledge C. Billstrand, K. Naughton, M. Soliai, and R. Nicolae for assistance with sample processing; R. Nasim, S. Chinthala, and R. Loth for help with sample collection; R. Minhas for help with clinical questions and data entry; and B. Furner and S. Choi for designing and maintaining the sample tracking database. ALSPAC GWAS data: We are grateful to all the families who took part in this study, the midwives for help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses The UChicago-Northwestern-Duke Prematurity Research Center was supported by a research grant from the March of Dimes to C.O., M.A.N., G.E.C., and J.K. This work was also supported by the March of Dimes Prematurity Research Center Ohio Collaborative and Bill and Melinda Gates Foundation (OPP1113966) to L.J.M. and G.Z. The UK Medical Research Council and Wellcome (grant reference 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grantacknowledgements.pdf). This research was specifically funded by Wellcome Trust WT088806 (Maternal genotype). This work was partially funded from grants from the National Institutes of Health, R01HL129735 (C.O.), 1R01MH110531 (X.H.), R01HL128075, R01119577, and R01DK114661 (M.A.N.)

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Sakabe, N. J., Aneas, I., Knoblauch, N., Sobreira, D. R., Clark, N., Paz, C., Horth, C., Ziffra, R., Kaur, H., Liu, X., Anderson, R., Morrison, J., Cheung, V. C., Grotegut, C., Reddy, T. E., Jacobsson, B., Hallman, M., Teramo, K., Murtha, A., ... Nóbrega, M. A. (2020). Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth. Science Advances, 6(49), Article eabc8696. https://doi.org/10.1126/sciadv.abc8696

@article{7d2d7281aa624de799ba108c28f69731,

title = "Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth",

abstract = "While a genetic component of preterm birth (PTB) has long been recognized and recently mapped by genome-wide association studies (GWASs), the molecular determinants underlying PTB remain elusive. This stems in part from an incomplete availability of functional genomic annotations in human cell types relevant to pregnancy and PTB. We generated transcriptome (RNA-seq), epigenome (ChIP-seq of H3K27ac, H3K4me1, and H3K4me3 histone modifications), open chromatin (ATAC-seq), and chromatin interaction (promoter capture Hi-C) annotations of cultured primary decidua-derived mesenchymal stromal/stem cells and in vitro differentiated decidual stromal cells and developed a computational framework to integrate these functional annotations with results from a GWAS of gestational duration in 56,384 women. Using these resources, we uncovered additional loci associated with gestational duration and target genes of associated loci. Our strategy illustrates how functional annotations in pregnancy-relevant cell types aid in the experimental follow-up of GWAS for PTB and, likely, other pregnancy-related conditions.",

author = "Sakabe, {Noboru J.} and Ivy Aneas and Nicholas Knoblauch and Sobreira, {Debora R.} and Nicole Clark and Cristina Paz and Cynthia Horth and Ryan Ziffra and Harjot Kaur and Xiao Liu and Rebecca Anderson and Jean Morrison and Cheung, {Virginia C.} and Chad Grotegut and Reddy, {Timothy E.} and Bo Jacobsson and Mikko Hallman and Kari Teramo and Amy Murtha and John Kessler and William Grobman and Ge Zhang and Muglia, {Louis J.} and Sarosh Rana and Lynch, {Vincent J.} and Crawford, {Gregory E.} and Carole Ober and Xin He and N{\'o}brega, {Marcelo A.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2020 The Authors,",

year = "2020",

month = dec,

day = "2",

doi = "10.1126/sciadv.abc8696",

language = "English (US)",

volume = "6",

journal = "Science Advances",

issn = "2375-2548",

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Sakabe, NJ, Aneas, I, Knoblauch, N, Sobreira, DR, Clark, N, Paz, C, Horth, C, Ziffra, R, Kaur, H, Liu, X, Anderson, R, Morrison, J, Cheung, VC, Grotegut, C, Reddy, TE, Jacobsson, B, Hallman, M, Teramo, K, Murtha, A, Kessler, J, Grobman, W, Zhang, G, Muglia, LJ, Rana, S, Lynch, VJ, Crawford, GE, Ober, C, He, X & Nóbrega, MA 2020, 'Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth', Science Advances, vol. 6, no. 49, eabc8696. https://doi.org/10.1126/sciadv.abc8696

TY - JOUR

T1 - Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth

AU - Sakabe, Noboru J.

AU - Aneas, Ivy

AU - Knoblauch, Nicholas

AU - Sobreira, Debora R.

AU - Clark, Nicole

AU - Paz, Cristina

AU - Horth, Cynthia

AU - Ziffra, Ryan

AU - Kaur, Harjot

AU - Liu, Xiao

AU - Anderson, Rebecca

AU - Morrison, Jean

AU - Cheung, Virginia C.

AU - Grotegut, Chad

AU - Reddy, Timothy E.

AU - Jacobsson, Bo

AU - Hallman, Mikko

AU - Teramo, Kari

AU - Murtha, Amy

AU - Kessler, John

AU - Grobman, William

AU - Zhang, Ge

AU - Muglia, Louis J.

AU - Rana, Sarosh

AU - Lynch, Vincent J.

AU - Crawford, Gregory E.

AU - Ober, Carole

AU - He, Xin

AU - Nóbrega, Marcelo A.

PY - 2020/12/2

Y1 - 2020/12/2

N2 - While a genetic component of preterm birth (PTB) has long been recognized and recently mapped by genome-wide association studies (GWASs), the molecular determinants underlying PTB remain elusive. This stems in part from an incomplete availability of functional genomic annotations in human cell types relevant to pregnancy and PTB. We generated transcriptome (RNA-seq), epigenome (ChIP-seq of H3K27ac, H3K4me1, and H3K4me3 histone modifications), open chromatin (ATAC-seq), and chromatin interaction (promoter capture Hi-C) annotations of cultured primary decidua-derived mesenchymal stromal/stem cells and in vitro differentiated decidual stromal cells and developed a computational framework to integrate these functional annotations with results from a GWAS of gestational duration in 56,384 women. Using these resources, we uncovered additional loci associated with gestational duration and target genes of associated loci. Our strategy illustrates how functional annotations in pregnancy-relevant cell types aid in the experimental follow-up of GWAS for PTB and, likely, other pregnancy-related conditions.

AB - While a genetic component of preterm birth (PTB) has long been recognized and recently mapped by genome-wide association studies (GWASs), the molecular determinants underlying PTB remain elusive. This stems in part from an incomplete availability of functional genomic annotations in human cell types relevant to pregnancy and PTB. We generated transcriptome (RNA-seq), epigenome (ChIP-seq of H3K27ac, H3K4me1, and H3K4me3 histone modifications), open chromatin (ATAC-seq), and chromatin interaction (promoter capture Hi-C) annotations of cultured primary decidua-derived mesenchymal stromal/stem cells and in vitro differentiated decidual stromal cells and developed a computational framework to integrate these functional annotations with results from a GWAS of gestational duration in 56,384 women. Using these resources, we uncovered additional loci associated with gestational duration and target genes of associated loci. Our strategy illustrates how functional annotations in pregnancy-relevant cell types aid in the experimental follow-up of GWAS for PTB and, likely, other pregnancy-related conditions.

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JF - Science Advances

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ER -

Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth

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