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

Dorota Zawada; Jessica Kornherr; Anna B. Meier; Gianluca Santamaria; Tatjana Dorn; Monika Nowak-Imialek; Daniel Ortmann; Fangfang Zhang; Mark Lachmann; Martina Dreßen; Mariaestela Ortiz; Victoria L. Mascetti; Stephen C. Harmer; Muriel Nobles; Andrew Tinker; Maria Teresa De Angelis; Roger A. Pedersen; Phillip Grote; Karl Ludwig Laugwitz; Alessandra Moretti; Alexander Goedel

doi:10.1038/s41467-023-36764-x

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

Dorota Zawada
, Jessica Kornherr
, Anna B. Meier
, Gianluca Santamaria
, Tatjana Dorn
, Monika Nowak-Imialek
, Daniel Ortmann
, Fangfang Zhang
, Mark Lachmann
, Martina Dreßen
, Mariaestela Ortiz
, Victoria L. Mascetti
, Stephen C. Harmer
, Muriel Nobles
, Andrew Tinker
, Maria Teresa De Angelis
, Roger A. Pedersen
, Phillip Grote
, Karl Ludwig Laugwitz
, Alessandra Moretti

Alexander Goedel

Technical University of Munich
Partner Site Munich Heart Alliance
University Magna Graecia of Catanzaro
Department of Surgery
University of Cambridge
Bristol Medical School
University of Bristol
Barts and The London School of Medicine and Dentistry
Stanford University School of Medicine
Institute for Biomedical Research
Johann Wolfgang Goethe University
Yale University Medical School
Karolinska Institutet

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

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.

Original language	English
Article number	1722
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-36764-x
State	Published - Dec 2023

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SDG 3 Good Health and Well-being

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Zawada, D., Kornherr, J., Meier, A. B., Santamaria, G., Dorn, T., Nowak-Imialek, M., Ortmann, D., Zhang, F., Lachmann, M., Dreßen, M., Ortiz, M., Mascetti, V. L., Harmer, S. C., Nobles, M., Tinker, A., De Angelis, M. T., Pedersen, R. A., Grote, P., Laugwitz, K. L., ... Goedel, A. (2023). Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools. Nature Communications, 14(1), Article 1722. https://doi.org/10.1038/s41467-023-36764-x

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title = "Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools",

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.",

author = "Dorota Zawada and Jessica Kornherr and Meier, \{Anna B.\} and Gianluca Santamaria and Tatjana Dorn and Monika Nowak-Imialek and Daniel Ortmann and Fangfang Zhang and Mark Lachmann and Martina Dre{\ss}en and Mariaestela Ortiz and Mascetti, \{Victoria L.\} and Harmer, \{Stephen C.\} and Muriel Nobles and Andrew Tinker and \{De Angelis\}, \{Maria Teresa\} and Pedersen, \{Roger A.\} and Phillip Grote and Laugwitz, \{Karl Ludwig\} and Alessandra Moretti and Alexander Goedel",

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doi = "10.1038/s41467-023-36764-x",

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Zawada, D, Kornherr, J, Meier, AB, Santamaria, G, Dorn, T, Nowak-Imialek, M, Ortmann, D, Zhang, F, Lachmann, M, Dreßen, M, Ortiz, M, Mascetti, VL, Harmer, SC, Nobles, M, Tinker, A, De Angelis, MT, Pedersen, RA, Grote, P, Laugwitz, KL , Moretti, A & Goedel, A 2023, 'Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools', Nature Communications, vol. 14, no. 1, 1722. https://doi.org/10.1038/s41467-023-36764-x

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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

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.

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ER -

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

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