ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
cAMP/EPAC Signaling Enables ETV2 to Induce Endothelial Cells with High Angiogenesis Potential.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 46 citations in OpenAlex.
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- Direct in vivo reprogramming to relieve tissue ischemia via induced vasculogenesis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Mechanism of disturbed endothelial cell function on angiogenesis following ischemic brain stroke (Review).Experimental and therapeutic medicine · 2025Review
- Systematic exploration of prognostic alternative splicing events related to tumor immune microenvironment of Clear Cell Renal Cell Carcinoma.Cancer biomarkers : section A of Disease markers · 2025Article
- Transcriptomics reveals dynamic changes in the "gene profiles" of rat supraspinatus tendon at three different time points after diabetes induction.BMC medical genomics · 2024Article
- Generation of Directly Reprogrammed Human Endothelial Cells.Methods in molecular biology (Clifton, N.J.) · 2024Article
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- Endothelial cell direct reprogramming: Past, present, and future.Journal of molecular and cellular cardiology · 2023Review
- Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation.Nature communications · 2023Article
- Updated Perspectives on Direct Vascular Cellular Reprogramming and Their Potential Applications in Tissue Engineered Vascular Grafts.Journal of functional biomaterials · 2022Review
- Generation and Application of Directly Reprogrammed Endothelial Cells.Korean circulation journal · 2022Review
- Review
- Inflammation-Mediated Angiogenesis in Ischemic Stroke.Frontiers in cellular neuroscience · 2021Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the generation of ETV2-induced endothelial cells (iECs) from human fibroblasts serves as a novel therapeutic strategy in regenerative medicine, the process is inefficient, resulting in incomplete iEC angiogenesis. Therefore, we employed chromatin immunoprecipitation (ChIP) sequencing and identified molecular mechanisms underlying ETV2-mediated endothelial transdifferentiation to efficiently produce iECs retaining appropriate functionality in long-term culture. We revealed that the majority of ETV2 targets in human fibroblasts are related to vasculature development and signaling transduction pathways, including Rap1 signaling. From a screening of signaling pathway modulators, we confirmed that forskolin facilitated efficient and rapid iEC reprogramming via activation of the cyclic AMP (cAMP)/exchange proteins directly activated by cAMP (EPAC)/RAP1 axis. The iECs obtained via cAMP signaling activation showed superior angiogenesis in vivo as well as in vitro. Moreover, these cells could form aligned endothelium along the vascular lumen ex vivo when seeded into decellularized liver scaffold. Overall, our study provided evidence that the cAMP/EPAC/RAP1 axis is required for the efficient generation of iECs with angiogenesis potential.
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