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Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Jennings, Rachel E 
Berry, Andrew A 
Gerrard, David T 
Wearne, Stephen J 
Strutt, James 

Abstract

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.

Description

Keywords

RNA sequencing, development, embryo, human, liver, pancreas, stem cell, transcriptome, Cell Differentiation, Gene Expression Profiling, Gene Expression Regulation, Developmental, Human Embryonic Stem Cells, Humans, Liver, Pancreas, Transcription Factors, Transcriptional Activation, Transcriptome

Journal Title

Stem Cell Reports

Conference Name

Journal ISSN

2213-6711
2213-6711

Volume Title

9

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MC_PC_12009)
This project received support from the UK Medical Research Council (MRC) (R.E.J. was a clinical research training fellow; additional funding from MR/L009986/1 to N.B. and N.A.H.; and MR/J003352/1 to K.P.H.), the Academy of Medical Sciences (supported by Wellcome Trust, MRC, British Heart Foundation, Arthritis Research UK, the Royal College of Physicians and Diabetes UK) (R.E.J.), the Society for Endocrinology (R.E.J.), the Wellcome Trust (N.A.H. was a senior fellow in clinical science, 088566; additional support from grant 105610/Z/14/Z), and the British Council and JDRF (14BX15NHBG to N.A.H.).