Key result
Mapping cardiogenesis identifies TGFBI as a cardiac fibroblast marker and links ISL1 loss to neural fates.
Why the study?
Multipotent heart progenitors generate diverse cardiac lineages and represent potential therapeutic candidates, prompting the need to deeply characterize the progenitor stage of cardiac differentiation at single-cell resolution.
Provides single-cell resolution insights into early human heart development, identifying TGFBI as a cardiac fibroblast marker and highlighting the role of ISL1 in myogenic lineage commitment.
Should not guide stem cell therapies; leaves open TGFBI and ISL1 as targets for directed cardiogenesis pending in vivo validation.
A family of multipotent heart progenitors plays a central role in the generation of diverse myogenic and nonmyogenic lineages in the heart. Cardiac progenitors in particular play a significant role in lineages involved in disease, and have also emerged to be a strong therapeutic candidate. Based on this premise, we aimed to deeply characterize the progenitor stage of cardiac differentiation at a single-cell resolution. Integrated comparison with an embryonic 5-week human heart transcriptomic dataset validated lineage identities with their late stage in vitro counterparts, highlighting the relevance of an in vitro differentiation for progenitors that are developmentally too early to be accessed in vivo. We utilized trajectory mapping to elucidate progenitor lineage branching points, which are supported by RNA velocity. Nonmyogenic populations, including cardiac fibroblast-like cells and endoderm, were found, and we identified TGFBI as a candidate marker for human cardiac fibroblasts in vivo and in vitro. Both myogenic and nonmyogenic populations express ISL1, and its loss redirected myogenic progenitors into a neural-like fate. Our study provides important insights into processes during early heart development.
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Mononen et al. (2020) studied Cardiogenesis and early heart development. Single-cell transcriptomic trajectory mapping and ISL1 loss was evaluated on Progenitor lineage branching points and cell identities. Trajectory mapping of human embryonic stem cell cardiogenesis identified TGFBI as a candidate marker for cardiac fibroblasts and showed that loss of ISL1 redirects progenitors to a neural-like fate.
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