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An integrative transcriptomic atlas of organogenesis in human embryos

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 a...

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Autores principales: Gerrard, Dave T, Berry, Andrew A, Jennings, Rachel E, Piper Hanley, Karen, Bobola, Nicoletta, Hanley, Neil A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996651/
https://www.ncbi.nlm.nih.gov/pubmed/27557446
http://dx.doi.org/10.7554/eLife.15657
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author Gerrard, Dave T
Berry, Andrew A
Jennings, Rachel E
Piper Hanley, Karen
Bobola, Nicoletta
Hanley, Neil A
author_facet Gerrard, Dave T
Berry, Andrew A
Jennings, Rachel E
Piper Hanley, Karen
Bobola, Nicoletta
Hanley, Neil A
author_sort Gerrard, Dave T
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.15657.001
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spelling pubmed-49966512016-08-29 An integrative transcriptomic atlas of organogenesis in human embryos Gerrard, Dave T Berry, Andrew A Jennings, Rachel E Piper Hanley, Karen Bobola, Nicoletta Hanley, Neil A eLife Developmental Biology and Stem Cells 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. DOI: http://dx.doi.org/10.7554/eLife.15657.001 eLife Sciences Publications, Ltd 2016-08-24 /pmc/articles/PMC4996651/ /pubmed/27557446 http://dx.doi.org/10.7554/eLife.15657 Text en © 2016, Gerrard et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology and Stem Cells
Gerrard, Dave T
Berry, Andrew A
Jennings, Rachel E
Piper Hanley, Karen
Bobola, Nicoletta
Hanley, Neil A
An integrative transcriptomic atlas of organogenesis in human embryos
title An integrative transcriptomic atlas of organogenesis in human embryos
title_full An integrative transcriptomic atlas of organogenesis in human embryos
title_fullStr An integrative transcriptomic atlas of organogenesis in human embryos
title_full_unstemmed An integrative transcriptomic atlas of organogenesis in human embryos
title_short An integrative transcriptomic atlas of organogenesis in human embryos
title_sort integrative transcriptomic atlas of organogenesis in human embryos
topic Developmental Biology and Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996651/
https://www.ncbi.nlm.nih.gov/pubmed/27557446
http://dx.doi.org/10.7554/eLife.15657
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