RESUMEN
The mammalian heart is derived from multiple cell lineages; however, our understanding of when and how the diverse cardiac cell types arise is limited. We mapped the origin of the embryonic mouse heart at single-cell resolution using a combination of transcriptomic, imaging, and genetic lineage labeling approaches. This mapping provided a transcriptional and anatomic definition of cardiac progenitor types. Furthermore, it revealed a cardiac progenitor pool that is anatomically and transcriptionally distinct from currently known cardiac progenitors. Besides contributing to cardiomyocytes, these cells also represent the earliest progenitor of the epicardium, a source of trophic factors and cells during cardiac development and injury. This study provides detailed insights into the formation of early cardiac cell types, with particular relevance to the development of cell-based cardiac regenerative therapies.
Asunto(s)
Corazón/embriología , Mioblastos Cardíacos/metabolismo , Miocardio/citología , Pericardio/citología , Pericardio/embriología , Animales , Diferenciación Celular/genética , Perfilación de la Expresión Génica , Ratones , Mioblastos Cardíacos/clasificación , Mioblastos Cardíacos/citología , Miocitos Cardíacos/citología , Análisis de la Célula Individual , TranscriptomaRESUMEN
Realizing the promise of therapeutic cardiac regeneration requires the targeting of accessible cell sources to promote neomyogenesis for the injured heart. After initial trials with cardiac myocytes and skeletal muscle progenitor cells (myoblasts), the rapid advances of stem cell technology have established the feasibility of endogenous stem cells to serve as donor cells for cellular cardiomyoplasty. In particular, bone marrow-derived stem cells have a great potential for clinical application due to their extracardiac locale and capacity to give rise to functional cardiac myocytes. The recent identification of resident cardiac stem cells also offers the opportunity to regenerate the infarcted myocardium, using the cells from the heart for ex vivo expansion or as targets for in vivo induction. To this end, future advances in cellular cardiomyoplasty may likely be based on therapies stimulating the trophic/cellular interactions that direct exogenous/endogenous stem cell-mediated cardiac regeneration.
