Journal
STEM CELL REPORTS
Volume 9, Issue 5, Pages 1387-1394Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2017.09.018
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Funding
- UK Medical Research Council (MRC) [MR/L009986/1, MR/J003352/1]
- Academy of Medical Sciences (Wellcome Trust)
- Academy of Medical Sciences (MRC)
- Academy of Medical Sciences (British Heart Foundation)
- Academy of Medical Sciences (Arthritis Research UK)
- Academy of Medical Sciences (Royal College of Physicians and Diabetes UK)
- Society for Endocrinology
- Wellcome Trust [088566, 105610/Z/14/Z]
- British Council
- JDRF [14BX15NHBG]
- MRC [G1100420, MR/P023541/1, MR/J003352/1, MR/L009986/1] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [SGL015\\1012] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [1085978] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [1497458] Funding Source: researchfish
- Medical Research Council [G1100420, MC_PC_12009, MR/L009986/1, MR/P023541/1, MR/J003352/1] Funding Source: researchfish
- National Institute for Health Research [CL-2014-06-002] Funding Source: researchfish
- The British Council [14BX14NHBG] Funding Source: researchfish
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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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