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 P.
AU - Kwon, Chulan
N1 - Funding Information:
The authors thank Kwon laboratory members, A. Colas, Sanford Burnham Prebys Medical Discovery Institute, San Diego and L.A. Larsen, Copenhagen University, Denmark for critical reading and discussions. P.A. was supported by a grant from the Mirowski Family Foundation—the Mirowski Discovery Award for Cardiovascular Research. E.T. was supported by the Johns Hopkins School of Medicine Clinician Scientist Award. S.P.C was supported by a grant from St. Jude Medical through the Heart Rhythm Society Cardiac Pacing and Electrophysiology Fellowship Award. This work was
Funding Information:
supported by grants from NHLBI/NIH (R01HL111198), NICHD/NIH (R01HD086026), MSCRF (2015-MSCRFI-1622), AHA, and The Magic that Matters Fund to C.K.
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.
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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 -