IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36764-x.html
   My bibliography  Save this article

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

Author

Listed:
  • Dorota Zawada

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Jessica Kornherr

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Anna B. Meier

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Gianluca Santamaria

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health
    University “Magna Graecia”)

  • Tatjana Dorn

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Monika Nowak-Imialek

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Daniel Ortmann

    (University of Cambridge
    University of Cambridge)

  • Fangfang Zhang

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health)

  • Mark Lachmann

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance)

  • Martina Dreßen

    (Institute Insure - Technical University of Munich, School of Medicine and Health)

  • Mariaestela Ortiz

    (University of Cambridge)

  • Victoria L. Mascetti

    (Bristol Heart Institute, Bristol Medical School, Translational Health Sciences)

  • Stephen C. Harmer

    (University of Bristol)

  • Muriel Nobles

    (Queen Mary University of London)

  • Andrew Tinker

    (Queen Mary University of London)

  • Maria Teresa Angelis

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    University “Magna Graecia”)

  • Roger A. Pedersen

    (Stanford University)

  • Phillip Grote

    (Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy
    Goethe University)

  • Karl-Ludwig Laugwitz

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance)

  • Alessandra Moretti

    (Technical University of Munich, School of Medicine and Health
    German Center for Cardiovascular Research (DZHK), Munich Heart Alliance
    Technical University of Munich, School of Medicine and Health
    Yale University School of Medicine)

  • Alexander Goedel

    (Technical University of Munich, School of Medicine and Health
    Karolinska Institute)

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.

Suggested Citation

  • Dorota Zawada & Jessica Kornherr & Anna B. Meier & Gianluca Santamaria & Tatjana Dorn & Monika Nowak-Imialek & Daniel Ortmann & Fangfang Zhang & Mark Lachmann & Martina Dreßen & Mariaestela Ortiz & Vi, 2023. "Retinoic acid signaling modulation guides in vitro specification of human heart field-specific progenitor pools," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36764-x
    DOI: 10.1038/s41467-023-36764-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36764-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-36764-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. George C. Linderman & Jun Zhao & Manolis Roulis & Piotr Bielecki & Richard A. Flavell & Boaz Nadler & Yuval Kluger, 2022. "Zero-preserving imputation of single-cell RNA-seq data," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Alejandro Aguilera-Castrejon & Bernardo Oldak & Tom Shani & Nadir Ghanem & Chen Itzkovich & Sharon Slomovich & Shadi Tarazi & Jonathan Bayerl & Valeriya Chugaeva & Muneef Ayyash & Shahd Ashouokhi & Da, 2021. "Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis," Nature, Nature, vol. 593(7857), pages 119-124, May.
    3. T. Yvanka de Soysa & Sanjeev S. Ranade & Satoshi Okawa & Srikanth Ravichandran & Yu Huang & Hazel T. Salunga & Amelia Schricker & Antonio del Sol & Casey A. Gifford & Deepak Srivastava, 2019. "Single-cell analysis of cardiogenesis reveals basis for organ-level developmental defects," Nature, Nature, vol. 572(7767), pages 120-124, August.
    4. Peter Andersen & Emmanouil Tampakakis & Dennisse V. Jimenez & Suraj Kannan & Matthew Miyamoto & Hye Kyung Shin & Amir Saberi & Sean Murphy & Edrick Sulistio & Stephen P. Chelko & Chulan Kwon, 2018. "Precardiac organoids form two heart fields via Bmp/Wnt signaling," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    5. Tui Neri & Emilye Hiriart & Patrick P. van Vliet & Emilie Faure & Russell A. Norris & Batoul Farhat & Bernd Jagla & Julie Lefrancois & Yukiko Sugi & Thomas Moore-Morris & Stéphane Zaffran & Randolph S, 2019. "Human pre-valvular endocardial cells derived from pluripotent stem cells recapitulate cardiac pathophysiological valvulogenesis," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jeremy Lotto & Rebecca Cullum & Sibyl Drissler & Martin Arostegui & Victoria C. Garside & Bettina M. Fuglerud & Makenna Clement-Ranney & Avinash Thakur & T. Michael Underhill & Pamela A. Hoodless, 2023. "Cell diversity and plasticity during atrioventricular heart valve EMTs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Yichuan Cao & Xiamiao Zhao & Songming Tang & Qun Jiang & Sijie Li & Siyu Li & Shengquan Chen, 2024. "scButterfly: a versatile single-cell cross-modality translation method via dual-aligned variational autoencoders," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Hao Chen & Frederick J. King & Bin Zhou & Yu Wang & Carter J. Canedy & Joel Hayashi & Yang Zhong & Max W. Chang & Lars Pache & Julian L. Wong & Yong Jia & John Joslin & Tao Jiang & Christopher Benner , 2024. "Drug target prediction through deep learning functional representation of gene signatures," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Zhenchao Tang & Guanxing Chen & Shouzhi Chen & Jianhua Yao & Linlin You & Calvin Yu-Chian Chen, 2024. "Modal-nexus auto-encoder for multi-modality cellular data integration and imputation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Norika Liu & Naofumi Kawahira & Yasuhiro Nakashima & Haruko Nakano & Akiyasu Iwase & Yasunobu Uchijima & Mei Wang & Sean M. Wu & Susumu Minamisawa & Hiroki Kurihara & Atsushi Nakano, 2023. "Notch and retinoic acid signals regulate macrophage formation from endocardium downstream of Nkx2-5," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Shiman Zuo & Yuxin Wang & Hanjing Bao & Zehui Zhang & Nanfei Yang & Meng Jia & Qing Zhang & Ani Jian & Rong Ji & Lidan Zhang & Yan Lu & Yahong Huang & Pingping Shen, 2024. "Lipid synthesis, triggered by PPARγ T166 dephosphorylation, sustains reparative function of macrophages during tissue repair," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    7. Mariana A. Branco & Tiago P. Dias & Joaquim M. S. Cabral & Perpetua Pinto-do-Ó & Maria Margarida Diogo, 2022. "Human multilineage pro-epicardium/foregut organoids support the development of an epicardium/myocardium organoid," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    8. Nevin Witman & Chikai Zhou & Timm Häneke & Yao Xiao & Xiaoting Huang & Eduarde Rohner & Jesper Sohlmér & Niels Grote Beverborg & Miia L. Lehtinen & Kenneth R. Chien & Makoto Sahara, 2023. "Placental growth factor exerts a dual function for cardiomyogenesis and vasculogenesis during heart development," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    9. Gayan I. Balasooriya & David L. Spector, 2022. "Allele-specific differential regulation of monoallelically expressed autosomal genes in the cardiac lineage," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. Hyun Kim & Won Chang & Seok Joo Chae & Jong-Eun Park & Minseok Seo & Jae Kyoung Kim, 2024. "scLENS: data-driven signal detection for unbiased scRNA-seq data analysis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    11. Clara Guijarro & Solène Song & Benoit Aigouy & Raphaël Clément & Paul Villoutreix & Robert G. Kelly, 2024. "Single-cell morphometrics reveals T-box gene-dependent patterns of epithelial tension in the Second Heart field," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36764-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.