very interesting study:
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Albumin-free conditions to generate cardiac progenitors
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Epicardial cell differentiation is β-catenin dependent
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Given the essential roles of β-catenin during cardiac progenitor induction
from hPSCs, we conclude that β-catenin is required at multiple stages
of hPSC differentiation to epicardial cells via small-molecule modulation
of canonical Wnt signalling. Differences between our study and previous
reports, including the initial starting cardiac progenitor cells and the
exposure windows for signalling modulators, may account for their
conclusion that BMP4 signalling,
but not Wnt alone, is required for robust epicardial differentiation.
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In summary, our findings support a model of human epicardial development
in which small-molecule-mediated exogenous modulation of Wnt/β-catenin
signalling is sufficient for the specification of epicardial cells from hPSCs.
This finding is consistent with the report that DKK1 and DKK2 double-null mice
increase epicardial specification and display a hypercellular epicardium.
This completely defined, xeno-free epicardial differentiation platform is
compatible with current good manufacturing practice (cGMP) standards and can b
e employed to efficiently derive self-renewing epicardial cell lineages from hPSCs,
which can thereby provide insights into mechanisms of heart development, maturation
and response to cardiac injury. Moreover, we show that hPSC-derived epicardial
cells can invade the myocardium in an infarcted mouse model, suggesting potential
applications in cell-based heart regeneration. Our results also point to
TGF-β signalling as a regulator of epicardial cell self-renewal and differentiation,
indicating the potential of TGF-β signalling modulators in heart regeneration.
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http://www.nature.co...s41551-016-0003
