In vivo generation of post-infarct human cardiac muscle by laminin-promoted cardiovascular progenitors

ABSTRACT: This SuperSeries is composed of the SubSeries listed below and contains: bulk RNA-seq of two time series of a xeno-free human cardiomyocyte differentiation protocol starting from HS1001 and H1 hECSs until day 94 cardiomyocytes, single cell sequencing of cardiovascular progenitors (H1 and HS1001-derived cardiovascular progenitors at day 9 and 11) and bulk RNA-Seq of H1 hECSs that have been transferred to a LN-221 matrix. Regeneration of injured human heart muscle is limited and an unmet clinical need. There are no methods for the reproducible generation of clinical quality stem-cell-derived cardiovascular progenitors (CVPs). We identified laminin-221 (LN-221) as the most likely expressed cardiac laminin. We produced it as human recombinant protein, and showed that LN-221 promotes differentiation of pluripotent hESCs towards cardiomyocyte lineage and downregulates pluripotency and teratoma associated genes. We developed a chemically defined, xeno-free laminin-based differentiation protocol to generate CVPs. We show high reproducibility of the differentiation protocol using time-course bulk RNA sequencing developed from different hESC lines. Single-cell RNA sequencing of CVPs derived from hESC lines supported reproducibility and identified three main progenitor subpopulations. These CVPs were transplanted into myocardial infarction mice, where heart function was measured by echocardiogram and human heart muscle bundle formation was identified histologically. This method may provide clinical quality cells for use in regenerative cardiology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE100725 | GEO | 2019/03/21

REPOSITORIES: GEO