Abstract
The discovery of the first heart field (FHF) and the second heart field (SHF) led us to understand how cardiac lineages and structures arise during development. However, it remains unknown how they are specified. Here, we generate precardiac spheroids with pluripotent stem cells (PSCs) harboring GFP/RFP reporters under the control of FHF/SHF markers, respectively. GFP+ cells and RFP+ cells appear from two distinct areas and develop in a complementary fashion. Transcriptome analysis shows a high degree of similarities with embryonic FHF/SHF cells. Bmp and Wnt are among the most differentially regulated pathways, and gain- and loss-of-function studies reveal that Bmp specifies GFP+ cells and RFP+ cells via the Bmp/Smad pathway and Wnt signaling, respectively. FHF/SHF cells can be isolated without reporters by the surface protein Cxcr4. This study provides novel insights into understanding the specification of two cardiac origins, which can be leveraged for PSC-based modeling of heart field/chamber-specific disease.
| Original language | English (US) |
|---|---|
| Article number | 3140 |
| Journal | Nature Communications |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2018 |
Fingerprint
ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
Precardiac organoids form two heart fields via Bmp/Wnt signaling. / Andersen, Peter; Tampakakis, Emmanouil; Jimenez, Dennisse V.; Kannan, Suraj; Miyamoto, Matthew; Shin, Hye Kyung; Saberi, Amir; Murphy, Sean; Sulistio, Edrick; Chelko, Stephen; Kwon, Chulan.
In: Nature Communications, Vol. 9, No. 1, 3140, 01.12.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Precardiac organoids form two heart fields via Bmp/Wnt signaling
AU - Andersen, Peter
AU - Tampakakis, Emmanouil
AU - Jimenez, Dennisse V.
AU - Kannan, Suraj
AU - Miyamoto, Matthew
AU - Shin, Hye Kyung
AU - Saberi, Amir
AU - Murphy, Sean
AU - Sulistio, Edrick
AU - Chelko, Stephen
AU - Kwon, Chulan
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The discovery of the first heart field (FHF) and the second heart field (SHF) led us to understand how cardiac lineages and structures arise during development. However, it remains unknown how they are specified. Here, we generate precardiac spheroids with pluripotent stem cells (PSCs) harboring GFP/RFP reporters under the control of FHF/SHF markers, respectively. GFP+ cells and RFP+ cells appear from two distinct areas and develop in a complementary fashion. Transcriptome analysis shows a high degree of similarities with embryonic FHF/SHF cells. Bmp and Wnt are among the most differentially regulated pathways, and gain- and loss-of-function studies reveal that Bmp specifies GFP+ cells and RFP+ cells via the Bmp/Smad pathway and Wnt signaling, respectively. FHF/SHF cells can be isolated without reporters by the surface protein Cxcr4. This study provides novel insights into understanding the specification of two cardiac origins, which can be leveraged for PSC-based modeling of heart field/chamber-specific disease.
AB - The discovery of the first heart field (FHF) and the second heart field (SHF) led us to understand how cardiac lineages and structures arise during development. However, it remains unknown how they are specified. Here, we generate precardiac spheroids with pluripotent stem cells (PSCs) harboring GFP/RFP reporters under the control of FHF/SHF markers, respectively. GFP+ cells and RFP+ cells appear from two distinct areas and develop in a complementary fashion. Transcriptome analysis shows a high degree of similarities with embryonic FHF/SHF cells. Bmp and Wnt are among the most differentially regulated pathways, and gain- and loss-of-function studies reveal that Bmp specifies GFP+ cells and RFP+ cells via the Bmp/Smad pathway and Wnt signaling, respectively. FHF/SHF cells can be isolated without reporters by the surface protein Cxcr4. This study provides novel insights into understanding the specification of two cardiac origins, which can be leveraged for PSC-based modeling of heart field/chamber-specific disease.
UR - http://www.scopus.com/inward/record.url?scp=85051269777&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85051269777&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-05604-8
DO - 10.1038/s41467-018-05604-8
M3 - Article
C2 - 30087351
AN - SCOPUS:85051269777
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3140
ER -