LEFTY-PITX2 signaling pathway is critical for generation of mature and ventricular cardiac organoids in human pluripotent stem cell-derived cardiac mesoderm cells
- Authors
- Song, Myeong-Hwa; Choi, Seung-Cheol; Noh, Ji-Min; Joo, Hyung Joon; Park, Chi-Yeon; Cha, Jung-Joon; Ahn, Tae Hoon; Ko, Tae Hee; Choi, Jong-Il; Na, Ji Eun; Rhyu, Im Joo; Jang, Yongjun; Park, Yongdoo; Gim, Jeong-An; Kim, Jong-Hoon; Lim, Do-Sun
- Issue Date
- Nov-2021
- Publisher
- ELSEVIER SCI LTD
- Keywords
- Ventricular cardiac organoid; Cardiac mesoderm cells; Cardiac maturation; ECM-integrins; LEFTY-PITX2 signaling; Focal adhesion signaling
- Citation
- Biomaterials, v.278
- Indexed
- SCIE
SCOPUS
- Journal Title
- Biomaterials
- Volume
- 278
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/54668
- DOI
- 10.1016/j.biomaterials.2021.121133
- ISSN
- 0142-9612
1878-5905
- Abstract
- The generation of mature ventricular cardiomyocytes (CMs) resembling adult CMs from human pluripotent stem cells (hPSCs) is necessary for disease modeling and drug discovery. To investigate the effect of self-organizing capacity on the generation of mature cardiac organoids (COs), we generated cardiac mesoderm cell-derived COs (CMC-COs) and CM-derived COs (CM-COs) and evaluated COs. CMC-COs exhibited more organized sarcomere structures and mitochondria, well-arranged t-tubule structures, and evenly distributed intercalated discs. Increased expressions of ventricular CM, cardiac metabolic, t-tubule formation, K+ ion channel, and junctional markers were confirmed in CMC-COs. Mature ventricular-like function such as faster motion vector speed, decreased beats per min, increased peak-to-peak duration, and prolonged APD50 and APD90 were observed in CMC-COs. Transcriptional profiling revealed that extracellular matrix-integrin, focal adhesion, and LEFTY-PITX2 signaling pathways are upregulated in CMC-COs. LEFTY knockdown affected ECM-integrin-FA signaling pathways in CMC-COs. Here, we found that high self-organizing capacity of CMCs is critical for the generation of mature and ventricular COs. We also demonstrated that LEFTY-PITX2 signaling plays key roles for CM maturation and specification into ventricular-like CM subtype in CMC-COs. CMC-COs are an attractive resource for disease modeling and drug discovery.
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Collections - 5. Others > Medical Science Research Management Center > 1. Journal Articles
- 1. Basic Science > Department of Biomedical Engineering > 1. Journal Articles
- 1. Basic Science > Department of Anatomy > 1. Journal Articles
- 4. Research institute > Cardiovascular Research Institute > 1. Journal Articles
- 3. Graduate School > Graduate School > 1. Journal Articles
- 4. Research institute > Metabolic Syndrome Research Center > 1. Journal Articles
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