Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping

Ding-Jun Hao; Yue Qin; Shi-Jie Zhou; Bu-Huai Dong; Jun-Song Yang; Peng Zou; Li-Ping Wang; Yuan-Ting Zhao

doi:10.1016/j.jpha.2023.09.013

Volume 14 Issue 3

Mar. 2024

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Ding-Jun Hao, Yue Qin, Shi-Jie Zhou, Bu-Huai Dong, Jun-Song Yang, Peng Zou, Li-Ping Wang, Yuan-Ting Zhao. Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping[J]. Journal of Pharmaceutical Analysis, 2024, 14(3): 335-347. doi: 10.1016/j.jpha.2023.09.013

Citation:

Ding-Jun Hao, Yue Qin, Shi-Jie Zhou, Bu-Huai Dong, Jun-Song Yang, Peng Zou, Li-Ping Wang, Yuan-Ting Zhao. Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping[J]. Journal of Pharmaceutical Analysis, 2024, 14(3): 335-347. doi: 10.1016/j.jpha.2023.09.013

Citation:

Ding-Jun Hao, Yue Qin, Shi-Jie Zhou, Bu-Huai Dong, Jun-Song Yang, Peng Zou, Li-Ping Wang, Yuan-Ting Zhao. Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping[J]. Journal of Pharmaceutical Analysis, 2024, 14(3): 335-347. doi: 10.1016/j.jpha.2023.09.013

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Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping

doi: 10.1016/j.jpha.2023.09.013

a. Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China;
b. Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China;
c. Department of Cardiovascular Medicine, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China;
d. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China

Funds:

This study was supported by Shaanxi Province Natural Science Foundation, China (Grant No.: 2021JM-568).

Received Date: Apr. 07, 2023
Accepted Date: Sep. 18, 2023
Rev Recd Date: Jul. 08, 2023
Publish Date: Sep. 22, 2023

Abstract

Abstract

Hyaluronan and proteoglycan link protein 1 (Hapln1) supports active cardiomyogenesis in zebrafish hearts, but its regulation in mammal cardiomyocytes is unclear. This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) and an adult mouse model of myocardial infarction. HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models, respectively. Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration. The results showed that recombinant human Hapln1 (rhHapln1) promotes the proliferation of hiPSC-CMs in a dose-dependent manner. As a physical binding protein of Hapln1, versican interacted with Nodal growth differentiation factor (NODAL) and growth differentiation factor 11 (GDF11). GDF11, but not NODAL, was expressed by hiPSC-CMs. GDF11 expression was unaffected by rhHapln1 treatment. However, this molecule was required for rhHapln1-mediated activation of the transforming growth factor (TGF)-β/Drosophila mothers against decapentaplegic protein (SMAD)2/3 signaling in hiPSC-CMs, which stimulates cell dedifferentiation and proliferation. Recombinant mouse Hapln1 (rmHapln1) could induce cardiac regeneration in the adult mouse model of myocardial infarction. In addition, rmHapln1 induced hiPSC-CM proliferation. In conclusion, Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway. Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.
- Hapln1,
- Versican,
- GDF11,
- iPSC-CMs,
- Cardiomyocyte proliferation

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References(35)

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