A genome scale transcriptional regulatory model of the human placenta-Reference-Cited by-同舟云学术

A genome scale transcriptional regulatory model of the human placenta

Published:2024-06-28 Issue:26 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Paquette Alison¹²^ORCID,Ahuna Kylia³^ORCID,Hwang Yeon Mi⁴^ORCID,Pearl Jocelynn⁵^ORCID,Liao Hanna¹^ORCID,Shannon Paul⁴^ORCID,Kadam Leena³^ORCID,Lapehn Samantha²^ORCID,Bucher Matthew³^ORCID,Roper Ryan⁴^ORCID,Funk Cory⁴^ORCID,MacDonald James¹^ORCID,Bammler Theo¹^ORCID,Baloni Priyanka⁴^ORCID,Brockway Heather⁶,Mason W. Alex⁷,Bush Nicole⁸^ORCID,Lewinn Kaja Z.⁸,Karr Catherine J.¹^ORCID,Stamatoyannopoulos John¹⁹^ORCID,Muglia Louis J.¹⁰¹¹^ORCID,Jones Helen¹²^ORCID,Sadovsky Yoel¹³¹⁴^ORCID,Myatt Leslie³^ORCID,Sathyanarayana Sheela¹²,Price Nathan D.⁴¹⁵^ORCID

Affiliation:

1. University of Washington, Seattle, WA, USA.

2. Seattle Children’s Research Institute, Seattle, WA, USA.

3. Oregon Health and Sciences University, Portland, OR, USA.

4. Institute for Systems Biology, Seattle, WA, USA.

5. Tune Therapeutics, Seattle, WA, USA.

6. Department of Physiology and Aging, University of Florida, Gainesville, FL, USA.

7. University of Tennessee Health Sciences Center, Memphis, TN, USA.

8. University of California San Francisco, San Francisco, CA, USA.

9. The Altius Institute, Seattle, WA, USA.

10. The Burroughs Wellcome Fund, Research Triangle Park, NC, USA.

11. Cincinnati Children’s Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

12. University of Florida, Gainesville, FL, USA.

13. Magee Womens Research Institute, Pittsburgh, PA, USA.

14. University of Pittsburgh, Pittsburgh, PA, USA.

15. Thorne HealthTech, New York City, NY, USA.

Abstract

Gene regulation is essential to placental function and fetal development. We built a genome-scale transcriptional regulatory network (TRN) of the human placenta using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental samples to globally and quantitatively map transcription factor (TF)–target gene interactions. In an independent dataset, the TRN model predicted target gene expression with an out-of-sample R 2 greater than 0.25 for 73% of target genes. We performed siRNA knockdowns of four TFs and achieved concordance between the predicted gene targets in our TRN and differences in expression of knockdowns with an accuracy of >0.7 for three of the four TFs. Our final model contained 113,158 interactions across 391 TFs and 7712 target genes and is publicly available. We identified 29 TFs which were significantly enriched as regulators for genes previously associated with preterm birth, and eight of these TFs were decreased in preterm placentas.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adf3411

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