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Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Kornherr, Jessica 
Meier, Anna B 
Santamaria, Gianluca  ORCID logo  https://orcid.org/0000-0001-9284-7492
Dorn, Tatjana 

Abstract

Cardiogenesis relies on the precise spatiotemporal coordination of multiple progenitor populations. Understanding the specification and differentiation of these distinct progenitor pools during human embryonic development is crucial for advancing our knowledge of congenital cardiac malformations and designing new regenerative therapies. By combining genetic labelling, single-cell transcriptomics, and ex vivo human-mouse embryonic chimeras we uncovered that modulation of retinoic acid signaling instructs human pluripotent stem cells to form heart field-specific progenitors with distinct fate potentials. In addition to the classical first and second heart fields, we observed the appearance of juxta-cardiac field progenitors giving rise to both myocardial and epicardial cells. Applying these findings to stem-cell based disease modelling we identified specific transcriptional dysregulation in first and second heart field progenitors derived from stem cells of patients with hypoplastic left heart syndrome. This highlights the suitability of our in vitro differentiation platform for studying human cardiac development and disease.

Description

Keywords

Humans, Animals, Mice, Tretinoin, Heart, Myocardium, Pluripotent Stem Cells, Cell Differentiation, Myocytes, Cardiac

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

14

Publisher

Springer Science and Business Media LLC
Sponsorship
Deutsches Zentrum für Herz-Kreislaufforschung (Deutsches Zentrum für Herz-Kreislaufforschung e.V.) (81X3600607, FKZ 81Z0600601)
European Research Council (261053, 788381, grant 788381)
Deutsche Forschungsgemeinschaft (German Research Foundation) (Transregio Research Unit 267, Transregio Research Unit 152)