@article{2106, keywords = {induced pluripotent stem cells, Pluripotent Stem Cells, Regenerative Medicine}, author = {Anna B. Meier and Dorota Zawada and Maria Teresa De Angelis and Laura D. Martens and Gianluca Santamaria and Sophie Zengerle and Monika Nowak-Imialek and Jessica Kornherr and Fangfang Zhang and Qinghai Tian and Cordula M. Wolf and Christian Kupatt and Makoto Sahara and Peter Lipp and Fabian J. Theis and Julien Gagneur and Alexander Goedel and Karl-Ludwig Laugwitz and Tatjana Dorn and Alessandra Moretti}, title = {Epicardioid single-cell genomics uncovers principles of human epicardium biology in heart development and disease}, abstract = {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.}, year = {2023}, journal = {Nature Biotechnology}, pages = {1-14}, month = {2023-04-03}, issn = {1546-1696}, url = {https://www.nature.com/articles/s41587-023-01718-7}, doi = {10.1038/s41587-023-01718-7}, language = {en}, }