University of Oulu

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

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

Saved in:
Author: Sakabe, Noboru J.1; Aneas, Ivy1; Knoblauch, Nicholas1;
Organizations: 1Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
2Duke Univ, Ctr Genom & Computat Biol, Dept Pediat, Durham, NC 27705 USA.
3Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
4Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA.
5Northwestern Univ, Inst Stem Cell Med, Chicago, IL 60611 USA.
6Duke Univ Hlth Syst, Dept Obstet & Gynecol, Durham, NC 27713 USA.
7Duke Univ, Ctr Genom & Computat Biol, Dept Biostat & Bioinformat, Durham, NC 27708 USA.
8Univ Gothenberg, Dept Obstet & Gynecol, Gothenburg, Sweden.
9Inst Publ Hlth, Dept Genet & Bioinformat, Area Hlth Data & Digitalizat, Oslo, Norway.
10Oulu Univ Hosp, Dept Children & Adolescents, Oulu, Finland.
11Helsinki Univ Cent Hosp, Dept Obstet & Gynecol, Helsinki, Finland.
12Univ Helsinki, Helsinki, Finland.
13Duke Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, Sch Med, Durham, NC 27713 USA.
14UCSF, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA.
15Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
16Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Human Genet, Cincinnati, OH 45229 USA.
17Burroughs Wellcome Fund, Res Triangle Pk, NC 27709 USA.
18Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA.
19Univ Buffalo, Dept Biol Sci, Buffalo, NY 14260 USA.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202103106948
Language: English
Published: American Association for the Advancement of Science, 2020
Publish Date: 2021-03-10
Description:

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.

see all

Series: Science advances
ISSN: 2375-2548
ISSN-E: 2375-2548
ISSN-L: 2375-2548
Volume: 6
Issue: 49
Article number: eabc8696
DOI: 10.1126/sciadv.abc8696
OADOI: https://oadoi.org/10.1126/sciadv.abc8696
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
Subjects:
Funding: 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/grant-acknowledgements.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.).
Copyright information: © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
  https://creativecommons.org/licenses/by-nc/4.0/