> Detailanzeige
Bolesani, Emiliano
[Verfasser:in];
Bornhorst, Dorothee
[Verfasser:in];
Iyer, Lavanya M
[Verfasser:in];
Zawada, Dorota
[Verfasser:in];
Friese, Nina
[Verfasser:in];
Morgan, Michael
[Verfasser:in];
Lange, Lucas
[Verfasser:in];
Gonzalez, David M
[Verfasser:in];
Schrode, Nadine
[Verfasser:in];
Leffler, Andreas
[Verfasser:in];
Wunder, Julian
[Verfasser:in];
Franke, Annika
[Verfasser:in];
Drakhlis, Lika
[Verfasser:in];
Sebra, Robert
[Verfasser:in];
Schambach, Axel
[Verfasser:in];
Goedel, Alexander
[Verfasser:in];
Dubois, Nicole C
[Verfasser:in];
Dobreva, Gergana
[Verfasser:in];
Moretti, Alessandra
[Verfasser:in];
Zelaráyan, Laura C
[Verfasser:in];
Abdelilah-Seyfried, Salim
[Verfasser:in];
Zweigerdt, Robert
[Verfasser:in]
Transient stabilization of human cardiovascular progenitor cells from human pluripotent stem cells in vitro reflects stage-specific heart development in vivo
Teilen
Literatur-
verwaltung
Direktlink
Zur
Merkliste
Lösche von
Merkliste
Per Email teilen
Auf Twitter teilen
Auf Facebook teilen
Per Whatsapp teilen
- Medientyp: E-Artikel
- Titel: Transient stabilization of human cardiovascular progenitor cells from human pluripotent stem cells in vitro reflects stage-specific heart development in vivo
- Beteiligte: Bolesani, Emiliano [Verfasser:in]; Bornhorst, Dorothee [Verfasser:in]; Iyer, Lavanya M [Verfasser:in]; Zawada, Dorota [Verfasser:in]; Friese, Nina [Verfasser:in]; Morgan, Michael [Verfasser:in]; Lange, Lucas [Verfasser:in]; Gonzalez, David M [Verfasser:in]; Schrode, Nadine [Verfasser:in]; Leffler, Andreas [Verfasser:in]; Wunder, Julian [Verfasser:in]; Franke, Annika [Verfasser:in]; Drakhlis, Lika [Verfasser:in]; Sebra, Robert [Verfasser:in]; Schambach, Axel [Verfasser:in]; Goedel, Alexander [Verfasser:in]; Dubois, Nicole C [Verfasser:in]; Dobreva, Gergana [Verfasser:in]; Moretti, Alessandra [Verfasser:in]; Zelaráyan, Laura C [Verfasser:in]; Abdelilah-Seyfried, Salim [Verfasser:in]; Zweigerdt, Robert [Verfasser:in]
-
Erschienen:
July 2024
- Erschienen in: Cardiovascular research ; 120(2024), 11 vom: Juli, Seite 1295-1311
- Sprache: Englisch
- DOI: 10.1093/cvr/cvae118
- Identifikator:
- Entstehung:
-
Anmerkungen:
Veröffentlicht: 05. Juni 2024
- Beschreibung: 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.
- Zugangsstatus: Freier Zugang