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

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

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