An integrative transcriptomic atlas of organogenesis in human embryos

Author:

Gerrard Dave T1ORCID,Berry Andrew A1,Jennings Rachel E12,Piper Hanley Karen1,Bobola Nicoletta3,Hanley Neil A12ORCID

Affiliation:

1. Division of Diabetes, Endocrinology & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom

2. Endocrinology Department, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom

3. Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom

Abstract

Human organogenesis is when severe developmental abnormalities commonly originate. However, understanding this critical embryonic phase has relied upon inference from patient phenotypes and assumptions from in vitro stem cell models and non-human vertebrates. We report an integrated transcriptomic atlas of human organogenesis. By lineage-guided principal components analysis, we uncover novel relatedness of particular developmental genes across different organs and tissues and identified unique transcriptional codes which correctly predicted the cause of many congenital disorders. By inference, our model pinpoints co-enriched genes as new causes of developmental disorders such as cleft palate and congenital heart disease. The data revealed more than 6000 novel transcripts, over 90% of which fulfil criteria as long non-coding RNAs correlated with the protein-coding genome over megabase distances. Taken together, we have uncovered cryptic transcriptional programs used by the human embryo and established a new resource for the molecular understanding of human organogenesis and its associated disorders.

Funder

Wellcome Trust

British Council

Medical Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference28 articles.

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4. TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors;Cebola;Nature Cell Biology,2015

5. The evolution of lineage-specific regulatory activities in the human embryonic limb;Cotney;Cell,2013

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