TY - JOUR
T1 - Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools
AU - Zawada, Dorota
AU - Kornherr, Jessica
AU - Meier, Anna B.
AU - Santamaria, Gianluca
AU - Dorn, Tatjana
AU - Nowak-Imialek, Monika
AU - Ortmann, Daniel
AU - Zhang, Fangfang
AU - Lachmann, Mark
AU - Dreßen, Martina
AU - Ortiz, Mariaestela
AU - Mascetti, Victoria L.
AU - Harmer, Stephen C.
AU - Nobles, Muriel
AU - Tinker, Andrew
AU - De Angelis, Maria Teresa
AU - Pedersen, Roger A.
AU - Grote, Phillip
AU - Laugwitz, Karl Ludwig
AU - Moretti, Alessandra
AU - Goedel, Alexander
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85151719189&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-36764-x
DO - 10.1038/s41467-023-36764-x
M3 - Article
C2 - 37012244
AN - SCOPUS:85151719189
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1722
ER -
