MESP1 knock-down in human iPSC attenuates early vascular progenitor cell differentiation after completed primitive streak specification
| Autor: | Mads Thomassen, Sohrab Ayoubi, Mark Burton, Søren P. Sheikh, Bruce R. Conklin, Tilde Eskildsen, Ditte Caroline Andersen, Charlotte Harken Jensen, Mohammed A Mandegar |
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| Rok vydání: | 2019 |
| Předmět: |
Fetal Proteins
Myocardium/metabolism CD34 Medical and Health Sciences Mesoderm 0302 clinical medicine Induced Pluripotent Stem Cells/cytology Basic Helix-Loop-Helix Transcription Factors Myocytes Cardiac Developmental Helix-Loop-Helix Motifs/physiology Endothelial Progenitor Cells 0303 health sciences Primitive streak Helix-Loop-Helix Motifs Gene Expression Regulation Developmental Cell Differentiation Myocytes Cardiac/metabolism Biological Sciences Cell biology medicine.anatomical_structure T-Box Domain Proteins/metabolism IPSC CRISPR Differentiation MESP1 Cardiac Brachyury Primitive Streak Induced Pluripotent Stem Cells Vascular progenitor Biology 03 medical and health sciences medicine Cell Differentiation/physiology Homeodomain Proteins/metabolism Humans Transcription Factors/metabolism Cell Lineage Fetal Proteins/metabolism Progenitor cell Endothelial Progenitor Cells/cytology Molecular Biology Embryonic Stem Cells Primitive Streak/cytology 030304 developmental biology Progenitor Homeodomain Proteins Mesoderm/metabolism Myocytes Embryonic Stem Cells/cytology Basic Helix-Loop-Helix Transcription Factors/genetics Myocardium Cell Biology Gene Expression Regulation SNAI1 MIXL1 T-Box Domain Proteins Gene Expression Regulation Developmental/genetics 030217 neurology & neurosurgery Transcription Factors Developmental Biology |
| Zdroj: | Developmental biology, vol 445, iss 1 Eskildsen, TV; Ayoubi, S; Thomassen, M; Burton, M; Mandegar, MA; Conklin, BR; et al.(2018). MESP1 knock-down in human iPSC attenuates early vascular progenitor cell differentiation after completed primitive streak specification.. Developmental biology. doi: 10.1016/j.ydbio.2018.10.020. UCSF: Retrieved from: http://www.escholarship.org/uc/item/2g6527hn Eskildsen, T V, Ayoubi, S, Thomassen, M, Burton, M, Mandegar, M A, Conklin, B R, Jensen, C H, Andersen, D C & Sheikh, S P 2019, ' MESP1 knock-down in human iPSC attenuates early vascular progenitor cell differentiation after completed primitive streak specification ', Developmental Biology, vol. 445, no. 1, pp. 1-7 . https://doi.org/10.1016/j.ydbio.2018.10.020 |
| DOI: | 10.1016/j.ydbio.2018.10.020. |
| Popis: | MESP1 is a key transcription factor in development of early cardiovascular tissue and it is required for induction of the cardiomyocyte (CM) gene expression program, but its role in vascular development is unclear. Here, we used inducible CRISPRi knock-down of MESP1 to analyze the molecular processes of the early differentiation stages of human induced pluripotent stem cells into mesoderm and subsequently vascular progenitor cells. We found that expression of the mesodermal marker, BRACHYURY (encoded by T) was unaffected in MESP1 knock-down cells as compared to wild type cells suggesting timely movement through the primitive streak whereas another mesodermal marker MIXL1 was slightly, but significantly decreased. In contrast, the expression of the vascular cell surface marker KDR was decreased and CD31 and CD34 expression were substantially reduced in MESP1 knock-down cells supporting inhibition or delay of vascular specification. In addition, mRNA microarray data revealed several other altered gene expressions including the EMT regulating transcription factors SNAI1 and TWIST1, which were both significantly decreased indicating that MESP1 knock-down cells are less likely to undergo EMT during vascular progenitor differentiation. Our study demonstrates that while leaving primitive streak markers unaffected, MESP1 expression is required for timely vascular progenitor specification. Thus, MESP1 expression is essential for the molecular features of early CM, EC and VSMC lineage specification. |
| Databáze: | OpenAIRE |
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