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| Verfasst von: | Bolesani, Emiliano [VerfasserIn]  |
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| | Bornhorst, Dorothee [VerfasserIn] |
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| | Iyer, Lavanya M [VerfasserIn] |
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| | Zawada, Dorota [VerfasserIn] |
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| | Friese, Nina [VerfasserIn] |
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| | Morgan, Michael [VerfasserIn] |
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| | Lange, Lucas [VerfasserIn] |
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| | Gonzalez, David M [VerfasserIn] |
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| | Schrode, Nadine [VerfasserIn] |
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| | Leffler, Andreas [VerfasserIn] |
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| | Wunder, Julian [VerfasserIn] |
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| | Franke, Annika [VerfasserIn] |
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| | Drakhlis, Lika [VerfasserIn] |
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| | Sebra, Robert [VerfasserIn] |
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| | Schambach, Axel [VerfasserIn] |
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| | Goedel, Alexander [VerfasserIn] |
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| | Dubois, Nicole C [VerfasserIn] |
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| | Dobreva, Gergana [VerfasserIn] |
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| | Moretti, Alessandra [VerfasserIn] |
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| | Zelaráyan, Laura C [VerfasserIn] |
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| | Abdelilah-Seyfried, Salim [VerfasserIn] |
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| | Zweigerdt, Robert [VerfasserIn] |
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| Titel: | Transient stabilization of human cardiovascular progenitor cells from human pluripotent stem cells in vitro reflects stage-specific heart development in vivo |
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| Verf.angabe: | Emiliano Bolesani, Dorothee Bornhorst, Lavanya M Iyer, Dorota Zawada, Nina Friese, Michael Morgan, Lucas Lange, David M Gonzalez, Nadine Schrode, Andreas Leffler, Julian Wunder, Annika Franke, Lika Drakhlis, Robert Sebra, Axel Schambach, Alexander Goedel, Nicole C Dubois, Gergana Dobreva, Alessandra Moretti, Laura C Zelaráyan, Salim Abdelilah-Seyfried, and Robert Zweigerdt |
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| E-Jahr: | 2024 |
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| Jahr: | July 2024 |
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| Umfang: | 17 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Veröffentlicht: 05. Juni 2024 ; Gesehen am 26.11.2024 |
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| Titel Quelle: | Enthalten in: Cardiovascular research |
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| Ort Quelle: | Oxford : Oxford University Press, 1967 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 120(2024), 11 vom: Juli, Seite 1295-1311 |
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| ISSN Quelle: | 1755-3245 |
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| Abstract: | Understanding the molecular identity of human pluripotent stem cell (hPSC)-derived cardiac progenitors and mechanisms controlling their proliferation and differentiation is valuable for developmental biology and regenerative medicine.Here, we show that chemical modulation of histone acetyl transferases (by IQ-1) and WNT (by CHIR99021) synergistically enables the transient and reversible block of directed cardiac differentiation progression on hPSCs. The resulting stabilized cardiovascular progenitors (SCPs) are characterized by ISL1pos/KI-67pos/NKX2-5neg expression. In the presence of the chemical inhibitors, SCPs maintain a proliferation quiescent state. Upon small molecules, removal SCPs resume proliferation and concomitant NKX2-5 up-regulation triggers cell-autonomous differentiation into cardiomyocytes. Directed differentiation of SCPs into the endothelial and smooth muscle lineages confirms their full developmental potential typical of bona fide cardiovascular progenitors. Single-cell RNA-sequencing-based transcriptional profiling of our in vitro generated human SCPs notably reflects the dynamic cellular composition of E8.25-E9.25 posterior second heart field of mouse hearts, hallmarked by nuclear receptor sub-family 2 group F member 2 expression. Investigating molecular mechanisms of SCP stabilization, we found that the cell-autonomously regulated retinoic acid and BMP signalling is governing SCP transition from quiescence towards proliferation and cell-autonomous differentiation, reminiscent of a niche-like behaviour.The chemically defined and reversible nature of our stabilization approach provides an unprecedented opportunity to dissect mechanisms of cardiovascular progenitors’ specification and reveal their cellular and molecular properties. |
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| DOI: | doi:10.1093/cvr/cvae118 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1093/cvr/cvae118 |
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| | DOI: https://doi.org/10.1093/cvr/cvae118 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1909550590 |
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| Verknüpfungen: | → Zeitschrift |
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Transient stabilization of human cardiovascular progenitor cells from human pluripotent stem cells in vitro reflects stage-specific heart development in vivo / Bolesani, Emiliano [VerfasserIn]; July 2024 (Online-Ressource)
