Biological Sciences Division
Published December 2, 2020 | Version v1
Journal article Open

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

Creators

  • 1. University of Chicago
  • 2. Duke University
  • 3. Northwestern University
  • 4. University of Gothenberg
  • 5. Oulu University Hospital
  • 6. University of Helsinki
  • 7. Cincinnati Children's Hospital Medical Center

Description

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.

Data availability

All data generated or analyzed during this study are included in this published article and available at www.immport.org/shared/study/SDY1626. All the peaks sets, pcHi-C, read count, and TPM data are available. An expanded set of 2530 differentially expressed genes and sets of differential peaks called without statistically testing for fold change is also made available. Source code for the GWAS enrichment analyses can be found at https://github.com/CreRecombinase/ptb_workflowr. Blacklisted regions: http://mitra.stanford.edu/kundaje/akundaje/release/blacklists/hg19-human/. Price Lab website: https://data.broadinstitute.org/alkesgroup/LDSCORE/. Epigenome Roadmap data website: https://egg2.wustl.edu/roadmap/data/byFileType/peaks/consolidated/narrowPeak/ucsc_compatible/. Additional data related to this paper may be requested from the authors.

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Additional details

Identifiers

DOI
10.1126/sciadv.abc8696
Other
oai:uchicago.tind.io:11079

Funding

March of Dimes Foundation
March of Dimes Prematurity Research Center Ohio Collaborative

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Human Genetics, Obstetrics and Gynecology