Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos
Rachel E. Jennings, Andrew A. Berry, David T. Gerrard, Stephen J. Wearne, James Strutt, Sarah Withey, Mariya Chhatriwala, Karen Piper Hanley, Ludovic Vallier, Nicoletta Bobola, Neil A. Hanley'Correspondence information about the author Neil A. HanleyEmail the author Neil A. Hanley
Published Online: October 19, 2017
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Open access funded by Wellcome Trust
Article Info
Publication History
Published: October 19, 2017 Accepted: September 25, 2017
Received in revised form: September 22, 2017 Received: April 25, 2017
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Highlights
• Transcriptomic signatures at the inception of human liver and pancreas development
• Limited conservation of pancreas-enriched gene expression between human and mouse
• Human PSC protocols imply a dorsal rather than a ventral pancreatic program
• New pancreatic transcription factors imputed by differential analysis
Summary
To interrogate the alternative fates of pancreas and liver in the earliest stages of human organogenesis, we developed laser capture, RNA amplification, and computational analysis of deep sequencing. Pancreas-enriched gene expression was less conserved between human and mouse than for liver. The dorsal pancreatic bud was enriched for components of Notch, Wnt, BMP, and FGF signaling, almost all genes known to cause pancreatic agenesis or hypoplasia, and over 30 unexplored transcription factors. SOX9 and RORA were imputed as key regulators in pancreas compared with EP300, HNF4A, and FOXA family members in liver. Analyses implied that current in vitro human stem cell differentiation follows a dorsal rather than a ventral pancreatic program and pointed to additional factors for hepatic differentiation. In summary, we provide the transcriptional codes regulating the start of human liver and pancreas development to facilitate stem cell research and clinical interpretation without inter-species extrapolation.
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