Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos.
Berry, Andrew A
Gerrard, David T
Wearne, Stephen J
Piper Hanley, Karen
Hanley, Neil A
Stem cell reports
MetadataShow full item record
Jennings, R. E., Berry, A. A., Gerrard, D. T., Wearne, S. J., Strutt, J., Withey, S., Chhatriwala, M., et al. (2017). Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos.. Stem cell reports, 9 (5), 1387-1394. https://doi.org/10.1016/j.stemcr.2017.09.018
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 signalling, almost all genes known to cause pancreatic agenesis of 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.
Liver, Pancreas, Humans, Transcription Factors, Gene Expression Profiling, Cell Differentiation, Gene Expression Regulation, Developmental, Transcriptional Activation, Transcriptome, Human Embryonic Stem Cells
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.).
External DOI: https://doi.org/10.1016/j.stemcr.2017.09.018
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275740
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
Recommended or similar items
The following licence files are associated with this item: