Tissue microenvironment dictates the state of human iPSC-derived endothelial cells of distinct developmental origin in 3D cardiac microtissues
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Each tissue and organ in the body has its own type of vasculature. Here, we demonstrate that organotypic vasculature for the heart can be recreated in a three-dimensional cardiac microtissue (MT) model composed of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), cardiac fibroblasts (CFs), and endothelial cells (ECs). ECs in cardiac MTs upregulated expression of markers enriched in human intramyocardial ECs, including CD36, CLDN5, APLNR, NOTCH4, IGFBP3, and ARHGAP18. We further show that the local microenvironment largely dictates the organ-specific identity of hiPSC-derived ECs: we compared ECs derived from cardiac and paraxial mesoderm and found that, regardless of origin, they acquired similar identities upon integration into cardiac MTs. Overall, the results indicated that while the initial gene profile of ECs was dictated by developmental origin, this could be modified by the local tissue environment. This developmental "plasticity" in ECs has implications for multiple pathological and disease states.
Details
| Original language | English |
|---|---|
| Article number | 113611 |
| Journal | iScience |
| Volume | 28 |
| Issue number | 10 |
| Publication status | Published - 17 Oct 2025 |
| Peer-reviewed | Yes |
External IDs
| PubMedCentral | PMC12546991 |
|---|---|
| Scopus | 105017881651 |
Keywords
Research priority areas of TU Dresden
DFG Classification of Subject Areas according to Review Boards
Sustainable Development Goals
Keywords
- Developmental biology, Transcriptomics, Stem cells research