Sox17‐Mediated Conversion of Fibroblasts into Endothelial Cells and Erythroblasts Enhances Neovascularization after Myocardial Infarction

• DOI: 10.1096/fasebj.31.1_supplement.12.4
• Publication Date: 2023-11-26T17:16:59Z
• Authors: Lianghui Zhang; Ankit Jambusaria; Zhigang Hong; Glenn Marsboom; Yang Yuan; Peter Toth; Brittney‐Shea Her...; Asrar B Malik; Jalees Rehman
• Keywords: CD31; Lineage markers

The mechanisms underlying the de-differentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is known whether fibroblast recapitulates generation multipotent progenitors during embryonic development which give rise to hematopoietic cell lineages. Here we established role developmental transcription factor Sox17 in regulating bi-lineage via intermediate progenitor cells. CD34+ were generated following dermal by overexpression pluripotency factors. Sorted transdifferentiated induced (iECs) erythroblasts (iErythroblasts) using specific growth therapeutic potential was assessed an experimental model myocardial infarction. De-differentiation gave 8.72% ± 1.22% (n=6). Differentiation yielded 7.8 2.9% VE-cadherin+, 8.4 3.1% CD31+, 4.9 1.3% VE-cadherin+/CD31+ iECs exhibited barrier function proliferation. Flow cytometry demonstrated that 4.2% 0.8% undergoing erythroblast induction CD235a+. iErythroblasts expressed erythroid surface markers formed colonies. Endothelial dependent on upregulation whereas suppression instead directed towards fate. Overexpression enhanced EC differentiation as evidenced increased fraction VE-cadherin positive when compared GFP (50.9 3.4% vs. 6.1 2.3%, P<0.001). Depleting significantly formation colonies while scramble shRNA (49.7 5.5% 34.7 4.3%, P<0.05). Implantation these bi-potential immune-deficient NOD-SCID mice resulted micro-vessels derived from perfused with mouse erythrocytes. Cell implantation markedly improved vascularity cardiac after gives a Sox17-dependent manner. These findings identify state critical bifurcation point can be tuned generate blood vessels or erythrocytes salvage ischemic tissue. Support Funding Information RO1HL118068, RO1HL090152 T32HL007829 Overview differential progenitors.