An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

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Discovery of specific pancreas developmental regulators has accelerated in recent years. In contrast, the global regulatory programs controlling pancreas development are poorly understood compared to other organs or tissues like heart or blood. Decoding this regulatory logic may accelerate development of replacement organs from renewable sources like stem cells, but this goal requires identification of regulators and assessment of their functions on a global scale. To address this important challenge for pancreas biology, we combined purification of normal and mutant cells with genome-scale methods to generate and analyze expression profiles from developing pancreas cells. Our work revealed regulatory gene sets governing development of pancreas progenitor cells and their progeny. Our integrative approach nominated multiple pancreas developmental regulators, including suspected risk genes for human diabetes, which we validated by phenotyping mutant mice on a scale not previously reported. Selection of these candidate regulators was unbiased; thus it is remarkable that all were essential for pancreatic islet development. Thus, our studies provide a new heuristic resource for identifying genetic functions underlying pancreas development and diseases like diabetes mellitus.

Vyšlo v časopise: An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004645
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004645

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