Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305-5329, USA.
Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):12691-6. doi: 10.1073/pnas.1304507110. Epub 2013 Jul 12.
Developmental biology is challenged to reveal the function of numerous candidate genes implicated by recent genome-scale studies as regulators of organ development and diseases. Recapitulating organogenesis from purified progenitor cells that can be genetically manipulated would provide powerful opportunities to dissect such gene functions. Here we describe systems for reconstructing pancreas development, including islet β-cell and α-cell differentiation, from single fetal progenitor cells. A strict requirement for native genetic regulators of in vivo pancreas development, such as Ngn3, Arx, and Pax4, revealed the authenticity of differentiation programs in vitro. Efficient genetic screens permitted by this system revealed that Prdm16 is required for pancreatic islet development in vivo. Discovering the function of genes regulating pancreas development with our system should enrich strategies for regenerating islets for treating diabetes mellitus.
发育生物学面临的挑战是揭示大量候选基因的功能，这些基因是最近的全基因组研究表明的器官发育和疾病的调节因子。从可以遗传操作的纯化祖细胞中再现器官发生将为剖析这些基因功能提供强大的机会。在这里，我们描述了从单个胎儿祖细胞重建胰腺发育的系统，包括胰岛β细胞和α细胞的分化。体内胰腺发育的天然遗传调节因子（如 Ngn3、Arx 和 Pax4）的严格要求，揭示了体外分化程序的真实性。该系统允许进行高效的遗传筛选，揭示了 Prdm16 是体内胰岛发育所必需的。用我们的系统发现调节胰腺发育的基因的功能，应该会丰富用于治疗糖尿病的胰岛再生策略。
