European Commission logo
español español
CORDIS - Resultados de investigaciones de la UE
CORDIS
Contenido archivado el 2024-05-29

The LIM-homeodomain transcription factor islet-1 is a genetic marker for isolation and generation of cardiovascular progenitor cells

Objetivo

The purification, renewal and differentiation of native cardiac progenitors would form a mechanistic underpinning for unravelling steps for both cardiac lineage formation and regeneration, and their links to forms of congenital and adult cardiac diseases. Taking advantage of a developmental lineage marker for undifferentiated cardiogenic precursors as a requirement for a heart-specific origin, we have identified in the post-natal heart a novel cardiac cell type. The LIM-homeodomain transcription factor isle t-1 (isl1) marks a cell population that makes a substantial contribution to the embryonic heart. Tamoxifen-inducible Cre/lox technology enables selective marking of this progenitor cell population including its progeny, at a defined time, and purification to relative homogeneity. Co-culture studies with neonatal myocytes indicate that isl1+ cells display a highly efficient conversion to a mature cardiac phenotype. Our hypothesis is that isl1 is a unique marker to isolate a population of cardiac precursors f rom the intact heart that can differentiate in vitro into functioning myocytes and to generate cardiogenic precursors from mouse embryonic stem cell systems during cardiogenesis. Our specific aims are: 1) To determine therapeutic efficacy of isl1+ cardiobl asts by transplantation into normal and diseased myocardium utilizing mouse models. 2) To establish optimal conditions for generation and differentiation of isl1+ progenitors in the mouse embryonic stem cell system. 3) To identify specific molecular pathwa ys that drive the differentiation of isl1+ cardioblasts into specific cardiomyocyte cell lineages. (Laugwitz K-L, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin L, Cai C-L, Lu M, Reth M, Platoshyn O, Yuan J, Evans S & Chien KR. Postnatal isl1+ card ioblasts enter fully differentiated cardiomyocyte lineages. Nature 433: 647-653 (2005).

Palabras clave

Convocatoria de propuestas

FP6-2004-MOBILITY-8
Consulte otros proyectos de esta convocatoria

Coordinador

KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITÄT MÜNCHEN
Aportación de la UE
Sin datos
Dirección
Ismaninger Strasse 22
MÜNCHEN
Alemania

Ver en el mapa

Enlaces
Coste total
Sin datos