The Activation of the LIMK/Cofilin Signaling Pathway via Extracellular Matrix–Integrin Interactions Is Critical for the Generation of Mature and Vascularized Cardiac Organoidsopen access
- Authors
- Noh, Ji-Min; Choi, Seung-Cheol; Song, Myeong-Hwa; Kim, Kyung Seob; Jun, Seongmin; Park, Jae Hyoung; Kim, Ju Hyeon; Kim, Kyoungmi; Ko, Tae Hee; Choi, Jong-Il; Gim, Jeong-An; Kim, Jong-Hoon; Jang, Yongjun; Park, Yongdoo; Na, Ji Eun; Rhyu, Im Joo; Lim, Do-Sun
- Issue Date
- Aug-2023
- Publisher
- Multidisciplinary Digital Publishing Institute (MDPI)
- Keywords
- cardiac organoids; LIMK/Cofilin signaling; mature cardiac organoids; vascularized cardiac organoids
- Citation
- Cells, v.12, no.16
- Indexed
- SCIE
SCOPUS
- Journal Title
- Cells
- Volume
- 12
- Number
- 16
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/64038
- DOI
- 10.3390/cells12162029
- ISSN
- 2073-4409
2073-4409
- Abstract
- The generation of mature and vascularized human pluripotent stem cell-derived cardiac organoids (hPSC-COs) is necessary to ensure the validity of drug screening and disease modeling. This study investigates the effects of cellular aggregate (CA) stemness and self-organization on the generation of mature and vascularized hPSC-COs and elucidates the mechanisms underlying cardiac organoid (CO) maturation and vascularization. COs derived from 2-day-old CAs with high stemness (H-COs) and COs derived from 5-day-old CAs with low stemness (L-COs) were generated in a self-organized microenvironment via Wnt signaling induction. This study finds that H-COs exhibit ventricular, structural, metabolic, and functional cardiomyocyte maturation and vessel networks consisting of endothelial cells, smooth muscle cells, pericytes, and basement membranes compared to L-COs. Transcriptional profiling shows the upregulation of genes associated with cardiac maturation and vessel formation in H-COs compared with the genes in L-COs. Through experiments with LIMK inhibitors, the activation of ROCK-LIMK-pCofilin via ECM–integrin interactions leads to cardiomyocyte maturation and vessel formation in H-COs. Furthermore, the LIMK/Cofilin signaling pathway induces TGFβ/NODAL and PDGF pathway activation for the maturation and vascularization of H-COs. The study demonstrates for the first time that LIMK/Cofilin axis activation plays an important role in the generation of mature and vascularized COs. © 2023 by the authors.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 1. Basic Science > Department of Anatomy > 1. Journal Articles
- 1. Basic Science > Department of Biomedical Engineering > 1. Journal Articles
- 5. Others > Medical Science Research Management Center > 1. Journal Articles
- 4. Research institute > Cardiovascular Research Institute > 1. Journal Articles
- 1. Basic Science > Department of Physiology > 1. Journal Articles
- 4. Research institute > Metabolic Syndrome Research Center > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.