Organ Development

Modeling pancreas development with CRISPR

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Science  15 Jul 2016:
Vol. 353, Issue 6296, pp. 259-260
DOI: 10.1126/science.353.6296.259-g

Reprogramming cells from one fate to another enables researchers to generate and study rare cell types. Combining this approach with TALEN (transcription activator-like effector nuclease) and CRISPR/Cas genome-editing technologies opens the way to understanding transcriptional control of organ development. Zhu et al. used these methods to study pancreatic development and disease. With a direct differentiation protocol, 50- to 80%-definitive endoderm cells were generated, and transcription factors that are key to pancreatic development (PDX1, RFX6, PTF1A, GLIS3, MNX1, NGN3, HES1, and ARX) were systematically knocked out using CRISPR/Cas to generate mutant hESC lines. This work confirmed prior findings but also revealed that RFX6 regulates pancreatic progenitor number, that PDX1 is dosage-sensitive for pancreatic endocrine development, and that NGN3 has a divergent role in mice and humans.

Cell Stem Cell 18, 755 (2016).

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