Identification of Latrophilin-2, a Specific Cell-surface Marker for Cardiac Progenitor Cells, and its Functional Significance in Heart Development [RNA-Seq]

ABSTRACT: Background: Identification of a lineage-specific marker plays a pivotal role in understanding developmental process and is necessary to isolate a certain cell type with high purity for therapeutic purposes. Here, we report a new cardiac-specific marker and demonstrate its functional significance in cardiac development. Methods: When mouse pluripotent stem cells (PSCs) were stimulated with BMP4, Activin A, and bFGF, they differentiated into cardiac cells. To screen molecules expressed on cardiac progenitor cell (CPC) surfaces compared to those on undifferentiated PSCs, we isolated Flk1+/PdgfRa+ cells at differentiation day 4 and performed microarray analysis. Results: Among candidates, we identified a new G protein-coupled receptor, latrophilin-2 (Lphn2). Here, we report this new cardiac-specific surface marker, Lphn2, expressed specifically on CPCs and cardiomyocytes (CMCs) during mouse and human PSC differentiation in vitro and exclusively in the heart during mouse embryonic development. Lphn2 knockout in mice was embryonically lethal because of severe heart, but not vascular, defects. PSC-derived Lphn2+ cells, but not Lphn2- cells, differentiated into CMCs and regenerated the myocardium when transplanted into infarcted hearts. Transplanted Lphn2+ cells improved left ventricular systolic function and reduced infarct sizes. Analysis of the signaling pathway indicated that cyclin-dependent kinase 5 is downstream of Lphn2 and collaborates with Src kinase to induce P38MAP kinase phosphorylation, subsequently activating cardiac-related gene transcription. Conclusion: Lphn2 is a functionally significant cell-surface marker for cardiac progenitor and cardiomyocytes. These findings provide a valuable tool for isolating cardiomyogenic progenitors and CMCs from PSCs and shed light on heart development and regeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE102973 | GEO | 2018/12/31

REPOSITORIES: GEO