TY - JOUR
KW - induced pluripotent stem cells
KW - Pluripotent Stem Cells
KW - Regenerative Medicine
AU - Anna B. Meier
AU - Dorota Zawada
AU - Maria Teresa De Angelis
AU - Laura D. Martens
AU - Gianluca Santamaria
AU - Sophie Zengerle
AU - Monika Nowak-Imialek
AU - Jessica Kornherr
AU - Fangfang Zhang
AU - Qinghai Tian
AU - Cordula M. Wolf
AU - Christian Kupatt
AU - Makoto Sahara
AU - Peter Lipp
AU - Fabian J. Theis
AU - Julien Gagneur
AU - Alexander Goedel
AU - Karl-Ludwig Laugwitz
AU - Tatjana Dorn
AU - Alessandra Moretti
AB - The epicardium, the mesothelial envelope of the vertebrate heart, is the source of multiple cardiac cell lineages during embryonic development and provides signals that are essential to myocardial growth and repair. Here we generate self-organizing human pluripotent stem cell-derived epicardioids that display retinoic acid-dependent morphological, molecular and functional patterning of the epicardium and myocardium typical of the left ventricular wall. By combining lineage tracing, single-cell transcriptomics and chromatin accessibility profiling, we describe the specification and differentiation process of different cell lineages in epicardioids and draw comparisons to human fetal development at the transcriptional and morphological levels. We then use epicardioids to investigate the functional cross-talk between cardiac cell types, gaining new insights into the role of IGF2/IGF1R and NRP2 signaling in human cardiogenesis. Finally, we show that epicardioids mimic the multicellular pathogenesis of congenital or stress-induced hypertrophy and fibrotic remodeling. As such, epicardioids offer a unique testing ground of epicardial activity in heart development, disease and regeneration.
BT - Nature Biotechnology
DA - 2023-04-03
DO - 10.1038/s41587-023-01718-7
LA - en
N2 - The epicardium, the mesothelial envelope of the vertebrate heart, is the source of multiple cardiac cell lineages during embryonic development and provides signals that are essential to myocardial growth and repair. Here we generate self-organizing human pluripotent stem cell-derived epicardioids that display retinoic acid-dependent morphological, molecular and functional patterning of the epicardium and myocardium typical of the left ventricular wall. By combining lineage tracing, single-cell transcriptomics and chromatin accessibility profiling, we describe the specification and differentiation process of different cell lineages in epicardioids and draw comparisons to human fetal development at the transcriptional and morphological levels. We then use epicardioids to investigate the functional cross-talk between cardiac cell types, gaining new insights into the role of IGF2/IGF1R and NRP2 signaling in human cardiogenesis. Finally, we show that epicardioids mimic the multicellular pathogenesis of congenital or stress-induced hypertrophy and fibrotic remodeling. As such, epicardioids offer a unique testing ground of epicardial activity in heart development, disease and regeneration.
PY - 2023
SP - 1
EP - 14
T2 - Nature Biotechnology
TI - Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease
UR - https://www.nature.com/articles/s41587-023-01718-7
Y2 - 2023-09-15
SN - 1546-1696
ER -