Tissue microenvironment dictates the state of human iPSC-derived endothelial cells of distinct developmental origin in 3D cardiac microtissues

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Xu Cao - , Leiden University Medical Centre (LUMC) (Autor:in)
  • Maria Mircea - , Leiden University (Autor:in)
  • Sara Cascione - , Leiden University Medical Centre (LUMC) (Autor:in)
  • Atoosa Amel - , Leiden University Medical Centre (LUMC) (Autor:in)
  • Theano Tsikari - , Leiden University Medical Centre (LUMC) (Autor:in)
  • Francijna E van den Hil - , Leiden University Medical Centre (LUMC) (Autor:in)
  • Hailiang Mei - , Leiden University Medical Centre (LUMC) (Autor:in)
  • Katrin Neumann - , Engineering von Stammzellen (FoG) (Autor:in)
  • Anna Alemany - , Leiden University Medical Centre (LUMC) (Autor:in)
  • Konstantinos Anastassiadis - , Engineering von Stammzellen (FoG) (Autor:in)
  • Christine L Mummery - , Leiden University Medical Centre (LUMC) (Autor:in)
  • Stefan Semrau - , Leiden University (Autor:in)
  • Valeria V Orlova - , Leiden University Medical Centre (LUMC) (Autor:in)

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

OriginalspracheEnglisch
Aufsatznummer113611
FachzeitschriftiScience
Jahrgang28
Ausgabenummer10
PublikationsstatusVeröffentlicht - 17 Okt. 2025
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC12546991
Scopus 105017881651

Schlagworte

DFG-Fachsystematik nach Fachkollegium

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Developmental biology, Transcriptomics, Stem cells research