Dataset Information

Fate mapping RNA-sequencing reveal Malat1 regulates Sca1⁺ progenitor cells to vascular smooth muscle cells transition in vascular remodeling.

ABSTRACT: Regeneration of smooth muscle cells (SMCs) is vital in vascular remodeling. Sca1⁺ stem/progenitor cells (SPCs) can generate de novo smooth muscle cells after severe vascular injury during vessel repair and regeneration. However, the underlying mechanisms have not been conclusively determined. Here, we reported that lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was down-regulated in various vascular diseases including arteriovenous fistula, artery injury and atherosclerosis. Using genetic lineage tracing mice and veingraft mice surgery model, we found that suppression of lncRNA Malat1 promoted Sca1⁺ cells to differentiate into SMCs in vivo, resulting in excess SMC accumulation in neointima and vessel stenosis. Genetic ablation of Sca1⁺ cells attenuated venous arterialization and impaired vascular structure normalization, and thus, resulting in less Malat1 down-regulation. Single cell sequencing further revealed a fibroblast-like phenotype of Sca1⁺ SPCs-derived SMCs. Protein array sequencing and in vitro assays revealed that SMC regeneration from Sca1⁺ SPCs was regulated by Malat1 through miR125a-5p/Stat3 signaling pathway. These findings delineate the critical role of Sca1⁺ SPCs in vascular remodeling and reveal that lncRNA Malat1 is a key regulator and might serve as a novel biomarker or potential therapeutic target for vascular diseases.

SUBMITTER: Lyu L

PROVIDER: S-EPMC10079726 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fate mapping RNA-sequencing reveal Malat1 regulates Sca1<sup>+</sup> progenitor cells to vascular smooth muscle cells transition in vascular remodeling.

Lyu Lingxia L Li Zhoubin Z Wen Zuoshi Z He Yongchun Y Wang Xuliang X Jiang Liujun L Zhou Xuhao X Huang Chengchen C Wu Yutao Y Chen Ting T Guo Xiaogang X

Cellular and molecular life sciences : CMLS 20230406 5

Regeneration of smooth muscle cells (SMCs) is vital in vascular remodeling. Sca1<sup>+</sup> stem/progenitor cells (SPCs) can generate de novo smooth muscle cells after severe vascular injury during vessel repair and regeneration. However, the underlying mechanisms have not been conclusively determined. Here, we reported that lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was down-regulated in various vascular diseases including arteriovenous fistula, artery injury and at ...[more]

PMID: 37022488

Similar Datasets

Project description:IntroductionPluripotent stem cells have been used by various researchers to differentiate and characterize endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) for the clinical treatment of vascular injuries. Studies continue to differentiate and characterize the cells with higher vascularization potential and low risk of malignant transformation to the recipient. Unlike previous studies, this research aimed to differentiate induced pluripotent stem (iPS) cells into endothelial progenitor cells (EPCs) and VSMCs using a step-wise technique. This was achieved by elucidating the spatio-temporal expressions of the stage-specific genes and proteins during the differentiation process. The presence of highly expressed oncogenes in iPS cells was also investigated during the differentiation period.MethodsInduced PS cells were differentiated into lateral mesoderm cells (Flk1+). The Flk1+ populations were isolated on day 5.5 of the mesodermal differentiation period. Flk1+ cells were further differentiated into EPCs and VSMCs using VEGF165 and platelet-derived growth factor-BB (PDGF-BB), respectively, and then characterized using gene expression levels, immunocytochemistry (ICC), and western blot (WB) methods. During the differentiation steps, the expression levels of the marker genes and proto-oncogenic Myc and Klf4 genes were simultaneously studied.ResultsThe optimal time for the isolation of Flk1+ cells was on day 5.5. EPCs and VSMCs were differentiated from Flk1+ cells and characterized with EPC-specific markers, including Kdr, Pecam1, CD133, Cdh5, Efnb2, Vcam1; and VSMC-specific markers, including Acta2, Cnn1, Des, and Myh11. Differentiated cells were validated based on their temporal gene expressions, protein synthesis, and localization at certain time points. Significant decreases in Myc and Klf4 gene expression levels were observed during the EPCs and VSMC differentiation period.ConclusionEPCs and VSMCs were successfully differentiated from iPS cells and characterized by gene expression levels, ICC, and WB. We observed significant decreases in oncogene expression levels in the differentiated EPCs and VSMCs. In terms of safety, the described methodology provided a better safety margin. EPCs and VSMC obtained using this method may be good candidates for transplantation and vascular regeneration.

Dataset Information

Fate mapping RNA-sequencing reveal Malat1 regulates Sca1⁺ progenitor cells to vascular smooth muscle cells transition in vascular remodeling.

Publications

Fate mapping RNA-sequencing reveal Malat1 regulates Sca1<sup>+</sup> progenitor cells to vascular smooth muscle cells transition in vascular remodeling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Fate mapping RNA-sequencing reveal Malat1 regulates Sca1+ progenitor cells to vascular smooth muscle cells transition in vascular remodeling.

Publications

Fate mapping RNA-sequencing reveal Malat1 regulates Sca1<sup>+</sup> progenitor cells to vascular smooth muscle cells transition in vascular remodeling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Fate mapping RNA-sequencing reveal Malat1 regulates Sca1⁺ progenitor cells to vascular smooth muscle cells transition in vascular remodeling.