BS67 BCL-6B is a novel regulator of hipsc-based vascular cell lineage specification

• Published in: Heart (British Cardiac Society) Vol. 109; no. Suppl 3; p. A294
• Main Author: Liu, Chenxin
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Cardiovascular Society 02.06.2023; BMJ Publishing Group LTD
• Subjects: B cell lymphoma - 6b; Basic Science; Human induced pluripotent stem cell; Vascular lineage cells differentiation
• ISSN: 1355-6037; 1468-201X
• DOI: 10.1136/heartjnl-2023-BCS.280

Vascular endothelial cells (ECs) and vascular smooth muscle cells (SMCs) are the principal building blocks that constitute the mammalian vascular systems. Vascular cells are profoundly crucial in maintaining vascular health and functionalities, dysfunctions of vascular ECs/SMCs are considered one of the major contributors to the pathogenesis of cardiovascular diseases (CVDs). Despite many associated risk factors have been spotted over the years, a gap of knowledge still persisted regarding to the exact pathogenic mechanisms involving vascular cell dysfunction. Therefore, the establishment of an efficient, stable resource for phenotypically comparable ECs/SMCs could facilitate a more accessible approach for both basic research and clinical applicationsHere, we demonstrate a highly efficient, chemically defined approach for generating differentiated ECs and SMCs from human induced pluripotent stem cells (hiPSCs), which enabled screenings for lineage-specific genes through Next-Generation genomic sequencing. Additionally, we employed a range of In vitro and In vivo assays to determine the functional impact of lineage-specific genewe were able to identify B cell lymphoma‘6b (BCL-6b) as one of the crucial genes for governing EC-specific cell fate during lineage specification. Subsequently, it was revealed that BCL-6b inhibition via treatment with a small-molecule inhibitor - FX1, was detrimental to the outcome of EC lineage differentiation as indicated by significant changes in molecular profile and functional competencies In vitro. Additionally, In vivo zebrafish and mouse model also demonstrated significant regulatory effect of BCL-6b in governing vessel formation and EC-specific functionality.Collectively, our findings were sufficient in drawing attention to the indispensable role of BCL-6b in mediating EC lineage specification as well as EC-specific functional maturation both In vitro and In vivo, the precise mechanisms of action could be characterized further in future studies, with the intent to explore the therapeutic potentials of modulating BCL-6b activities in clinical treatment for cardiovascular diseases.Conflict of InterestN/A