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Identification and Characterization of the Presomitic Mesoderm Progenitor

前体中胚层祖细胞的鉴定和表征

基本信息

批准号：
8501607
负责人：
CRAIG E NELSON
金额：
$ 18.36万
依托单位：
UNIVERSITY OF CONNECTICUT STORRS
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8501607
关键词：
Affect Anatomy Arthritis Biology Blood Cardiovascular system Cartilage Cells Clinical Congenital Abnormality Connective Tissue Data Derivation procedure Disease Embryo Foundations Generations Goals Grant Hensen&apos s Node In Situ Hybridization In Vitro Knowledge Maintenance Mammals Mesoderm Mesoderm Cell Molecular Molecular Profiling Mus Muscle Musculoskeletal Musculoskeletal Diseases Osteoporosis Paraxial Mesoderm Pathway interactions Patients Population Primitive Streaks Procedures Protocols documentation Regenerative Medicine Role Signal Pathway Signal Transduction Skeletal Muscle Somites Stem cells Testing Tissues Transcript Tretinoin Wasting Syndrome Work Wound Healing base cell type embryonic stem cell human disease human embryonic stem cell improved induced pluripotent stem cell insight molecular marker novel strategies progenitor public health relevance regenerative single cell analysis tissue culture tissue regeneration

项目摘要

DESCRIPTION (provided by applicant): Diseases of the mesodermal tissues of the body including wound healing, arthritis, osteoporosis and muscular wasting diseases, affect millions of people across the globe. If existing barriers to the efficient derivation of mesodermal tissues from readily-available, patient-matched stem cells could be overcome, these diseases could be treated with stem cell-based regenerative medicine. Unfortunately, robust directed differentiation of mesoderm from embryonic stem cells (ESC) and induced pluripotent stem cells (IPSC) is currently limited to cardiovascular and blood derivatives. Reproducible protocols for the differentiation of muscle, cartilage, and connective tissues, or more specifically, those mesodermal derivatives produced solely from pre-somitic mesoderm (PSM), have yet to emerge. While it is possible to obtain some cell types of the posterior mesoderm from human ESC, these efficiencies (commonly <1%) must be vastly improved before regenerative procedures for these tissues will be feasible. Previous studies have indicated the presence of an endogenous PSM-progenitor (PSM-Pr) cell located at the border of the primitive streak and Hensen's node (the PSM-Pr niche). Progeny of the PSM-Pr colonize the paraxial mesoderm and give rise to the somites, which in turn produce the skeletal muscle, cartilage, and connective tissue of the embryo. The primary focus of the work described here is to identify and exhaustively characterize the cell types that comprise and maintain the endogenous progenitor stem cell and its niche. In this project we will (1) identify all cell types located in the border region and (2) evaluate the role of key signaling pathways in the maintenance of the PSM-Pr and the PSM-Pr niche. Successful completion of these goals will provide unprecedented insight into the generation of somitic mesoderm and enable novel approaches to the generation of therapeutically relevant mesodermal cell types for clinical use.

描述（由申请人提供）：身体中胚层组织的疾病，包括伤口愈合、关节炎、骨质疏松症和肌肉萎缩性疾病，影响着地球仪的数百万人。如果现有的障碍，有效地衍生中胚层组织从现成的，病人匹配的干细胞可以克服，这些疾病可以治疗干细胞为基础的再生医学。不幸的是，从胚胎干细胞（ESC）和诱导的多能干细胞（IPSC）稳健定向分化中胚层目前仅限于心血管和血液衍生物。用于分化肌肉、软骨和结缔组织，或更具体地说，仅由前体节中胚层（PSM）产生的那些中胚层衍生物的可再现方案尚未出现。虽然可以从人ESC获得后中胚层的一些细胞类型，但在这些组织的再生程序可行之前，必须大大提高这些效率（通常<1%）。以前的研究表明，存在一个内源性PSM祖细胞（PSM-Pr）细胞位于原始条纹和亨森结（PSM-Pr龛）的边界。PSM-Pr的后代定殖于近轴中胚层并产生体节，体节又产生胚胎的骨骼肌、软骨和结缔组织。本文所述工作的主要重点是鉴定和彻底表征包含和维持内源性祖干细胞及其小生境的细胞类型。在这个项目中，我们将（1）确定所有细胞类型位于边界区域和（2）评估关键信号通路在维持PSM-Pr和PSM-Pr生态位中的作用。这些目标的成功完成将为体节中胚层的产生提供前所未有的洞察力，并使新的方法能够产生用于临床用途的治疗相关的中胚层细胞类型。