Diversity and Specification of Pancreatic Progenitor Cells

祖细胞是一种未成熟的细胞类型，负责在 胚胎发育以及成年后补充和修复组织。理解 因此，祖细胞是生物学中的一个中心问题。这个问题适用于胰腺，它是人体的一个器官 对人体生理至关重要，因为消化酶和荷尔蒙的产生 作为胰岛素。本项目的长期目标是了解胰腺的多样性和发展。 为了设计出更好的治疗糖尿病等胰腺疾病的策略。 在这项建议的具体目标I中，我们将确定发育中的祖细胞的多样性。 通过基因组规模的表达分析来确定将标记每个 祖代种群。在特定目标II中，我们将确定两个特定的胰腺前体细胞的谱系 用突变小鼠品系进行遗传谱系追踪实验。在具体目标三中，我们将 转录因子如何调控不同祖细胞发育的功能测试假说 类型。 所提出的研究有望对胰腺的多样性和特异性提供重要的启示。 祖细胞。更好地了解胰腺前体细胞的生物学应该有助于努力 为治疗糖尿病的细胞替代疗法衍生具有功能的内分泌细胞。此外，这些研究 可能导致对成年胰腺祖细胞的更深入的了解，这些祖细胞可能被利用来进行再生 心理治疗。

Progenitor cells are immature cell types that are responsible for constructing the entire organism during embryonic development as well as for replenishing and repairing tissues in adult life. Understanding progenitor cells is therefore a central question in biology. This problem applies to the pancreas, an organ of vital importance to human physiology because of the production of digestive enzymes and hormones such as insulin. The long term goal of this project is to understand the diversity and development of pancreatic progenitor cells in order to devise better strategies to treat pancreatic diseases such as diabetes. In Specific Aim I of this proposal, we will determine the diversity of progenitor cells in the developing pancreas by a genome scale expression analysis to identify unique molecular markers that will mark each progenitor population. In Specific Aim II, we will determine the lineage of two specific pancreatic progenitor populations by genetic lineage tracing experiments with mutant mouse lines. In Specific Aim III,we will functionally test hypotheses of how transcription factors regulate the development of different progenitor cell types. The proposed studies are expected to shed important light on the diversity and specification of pancreatic progenitor cells. A better understanding of the biology of pancreatic progenitor cells should aid efforts to derive functional endocrine cells for cell replacement therapies to treat diabetes. In addition, these studies may lead to greater insights into adult pancreatic progenitors that may be exploited for regeneration based therapy.