Endothelial Arid1a deletion disrupts the balance among angiogenesis, neurogenesis and gliogenesis in the developing brain.

Yuanyuan Wang, Libo Su, Wenwen Wang, Jinyue Zhao, Yanyan Wang, Sihan Li, Yan Liu, Renjie Chai, Xin Li, Zhaoqian Teng, Changmei Liu, Baoyang Hu, Fen Ji, Jianwei Jiao

Cell proliferation 2023 May

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The vascular system and the neural system processes occur simultaneously, the interaction among them is fundamental to the normal development of the central nervous system. Arid1a (AT-rich interaction domain 1A), which encodes an epigenetic subunit of the SWI/SNF chromatin-remodelling complex, is associated with promoter-mediated gene regulation and histone modification. However, the molecular mechanism of the interaction between cerebrovascular and neural progenitor cells (NPCs) remains unclear. To generate Arid1acKO-Tie2 mice, Arid1afl/fl mice were hybridized with Tie2-Cre mice. The Angiogenesis, neurogenesis and gliogenesis were studied by immunofluorescence staining and Western blotting. RNA-seq, RT-PCR, Western blotting, CO-IP and rescue experiments were performed to dissect the molecular mechanisms of Arid1a regulates fate determination of NPCs. We found that the absence of Arid1a results in increased the density of blood vessels, delayed neurogenesis and decreased gliogenesis, even after birth. Mechanistically, the deletion of Arid1a in endothelial cells causes a significant increase in H3k27ac and the secretion of maternal protein 2 (MATN2). In addition, matn2 alters the AKT/SMAD4 signalling pathway through its interaction with the NPCs receptor EGFR, leading to the decrease of SMAD4. SMAD complex further mediates the expression of downstream targets, thereby promoting neurogenesis and inhibiting gliogenesis. This study suggests that endothelial Arid1a tightly controls fate determination of NPCs by regulating the AKT-SMAD signalling pathway. © 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.

Citation

Yuanyuan Wang, Libo Su, Wenwen Wang, Jinyue Zhao, Yanyan Wang, Sihan Li, Yan Liu, Renjie Chai, Xin Li, Zhaoqian Teng, Changmei Liu, Baoyang Hu, Fen Ji, Jianwei Jiao. Endothelial Arid1a deletion disrupts the balance among angiogenesis, neurogenesis and gliogenesis in the developing brain. Cell proliferation. 2023 May;56(5):e13447