权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Microenvironmental cues control pancreas cell fate and beta-cell maturation

微环境线索控制胰腺细胞命运和β细胞成熟

基本信息

批准号：
10445008
负责人：
Hung-Ping Shih
金额：
$ 40.82万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10445008
关键词：
Adult Affect Beta Cell Biochemical Biological Assay Biomedical Engineering Cell Culture Techniques Cell Differentiation process Cell Maturation Cell Therapy Cells Complex Couples Cues Defect Development Embryo Endocrine Exhibits Future Gene Expression Profiling Generations Glucose Goals Impairment In Vitro Insulin-Dependent Diabetes Mellitus Integrins Islets of Langerhans Knowledge Link Mechanics Methodology Molecular Morphogenesis Mus Organ Pancreas Pathway interactions Play Process Protocols documentation Psyche structure Role Signal Transduction Testing Therapeutic Tissues Translating Variant blood glucose regulation cell type endocrine pancreas development human pluripotent stem cell improved in vivo inhibitor insulin secretion islet islet stem cells mouse model nanofiber notch protein novel postnatal progenitor programs response scaffold stem cells

项目摘要

ABSTRACT Current strategies for treating type 1 diabetes via cell replacement are limited by a shortage of donor islets; human pluripotent stem cell (hPSC)-derived β (hPSC-β) cells represent a promising solution to this dilemma. To improve current methodologies for the differentiation of hPSCs towards functional β-cells, a comprehensive understanding of the molecular programs for the processes of endocrine development and β-cells maturation is still required. Our preliminary studies suggested that integrin signaling and microenvironment stiffness play an integral role in coordinating islet and β-cell development. The present proposal seeks to elucidate the role that integrin and microenvironment stiffness play in coordinating these complex processes. We aim to uncover the mechanisms of integrin signaling in controlling 1) endocrine cell fate decision, 2) islet development, and 3) β-cell maturation. We will utilize a combination of pancreas-, islet-, and β-cell-specific deletion mouse models to inactivate integrin subunit β1 (Itgb1, a subunit essential for integrin signaling). We also aim to promote in vitro maturation of hPSC-β cells by controlling the microenvironments stiffness. To achieve this, we established a novel cell culture platform for temporal control of microenvironment stiffness. By culturing and differentiating the hPSC-β progenitors on this platform, we will elucidate the role which microenvironment stiffness plays on β-cell maturation. Together, our study will provide a greater understanding of the role of integrin signaling and microenvironment stiffness in regulating β-cell development. This will inform future functional hPSC-β generation strategies.

摘要