| Tissue-specific lncRNA GATA6-AS1 and its ortholog Moshe as essential regulators of aortic valve development |
Najung Kim  1,2 (PHD student), Eun-Hye Moon3 (Doctor), Ji Hoon Oh1,2 (Doctor), Hyeon Myeong Kim4 (PHD student), Su Haeng Sung4 (Research worker), Han-Se Kim1,2 (PHD student), Yeo-Jin Im1,2 (PHD student), Chae-Yi Kim1,2 (Research worker), Jasmin E. Turner5 (PHD student), Young Jae Lee 3 (Professor), Yong Jun Kim 4 (Professor), Je Yeol Cho 1,2,* (Professor) |
1BK21 Plus and Research Institute for Veterinary Science, Department of Biochemistry, School of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.,
2Comparative Medicine Disease Research Center, Seoul National University, Seoul, Republic of Korea.,
3Lee Gil Ya Cancer and Diabetes Institute, Department of Biochemistry, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Republic of Korea.,
4Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.,
5Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom. |
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Abstract
Long noncoding RNAs (lncRNAs) play a crucial role in epigenetic regulation during cardiogenesis, yet their involvement in aortic valve disease remains poorly understood. Investigating lncRNAs expressed in the human embryonic heart and identifying their specific isoforms is particularly challenging due to technical and ethical constraints.
In this study, we identified GATA6-AS1 as a heart-enriched lncRNA by analyzing publicly available RNA sequencing data from human embryonic tissues. Using in vitro models and CS17 embryonic heart tissue, we found that GATA6-AS1 isoforms 202 and 208 are specifically expressed in cardiac neural crest lineage cells during aortic valve development. Similarly, we identified Moshe, the murine ortholog of GATA6-AS1, as being expressed during aortic valve formation in mice. Notably, Moshe depletion led to the development of bicuspid aortic valves (BAV), accompanied by a significant downregulation of BAV-related genes, particularly those involved in the Notch and TGF-モ signaling pathways.
These findings highlight the critical role of GATA6-AS1 in aortic valve development by studying its mouse ortholog Moshe and suggest that lncRNAs, which remain underexplored in congenital heart disease due to research limitations, may have significant implications for BAV pathogenesis and potential therapeutic strategies.
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| Abstract, Accepted Manuscript [Submitted on December 30, 2024, Accepted on February 28, 2025] |
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