Comparative analysis of BMP signaling in human ECFCs reveals vascular bed-dependent ALK2 expression.

Großmann, Nadine Z, Haştar, Nurcan, Xiao, Yunyun, Brakus, Indigo, Kampfrath, Branka, Bogaard, Harm-Jan, Szulcek, Robert, Medina, Reinhold J, Hildebrandt, Susanne and Knaus, Petra ORCID: 0000-0003-2492-1667 (2026) Comparative analysis of BMP signaling in human ECFCs reveals vascular bed-dependent ALK2 expression. Vascular biology (Bristol, England), 8 (1). VB250010-. ISSN 2516-5658, 2516-5658

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Abstract

<h4>Graphical abstract</h4><h4>Abstract</h4>Bone morphogenetic protein (BMP) signaling pathway components play a crucial role in cardiovascular homeostasis and sprouting angiogenesis. Endothelial colony-forming cells (ECFCs) are endothelial progenitor cells with a high proliferative and angiogenic capacity and therefore are valuable candidates for angiogenic therapies and vascular regeneration. Of note, a direct comparative analysis of human umbilical cord blood-derived ECFCs (CB-ECFCs) and peripheral blood-derived ECFCs (PB-ECFCs) with a focus on BMP signaling and potential tissue-dependent effects is lacking. In this study, we characterized the BMP signaling responses in ECFCs derived from the umbilical cord and peripheral blood. Analysis of SMAD1/5 phosphorylation showed that BMP2 stimulation only leads to an activation of the BMP signaling pathway in PB-ECFCs, but not in CB-ECFCs. Analysis of gene expression levels of BMP/TGF-β type I and type II receptors demonstrated an elevated expression of ALK2 in PB-ECFCs. Evaluation of sprouting angiogenesis revealed that si-RNA-mediated silencing of ALK2 in CB-ECFCs results in hypersprouting, while si-RNA-mediated silencing of ALK3 leads to hypersprouting in PB-ECFCs. To conclude, we found a differential BMP signaling pathway activation in CB-ECFCs and PB-ECFCs, which is related to vascular bed-dependent expression of ALK2.

Item Type:	Article
Uncontrolled Keywords:	ALK2, BMP signaling, ECFCs, endothelial progenitor cells, vascular bed
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Inst. Life Courses & Medical Sciences (T&R staff) Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Eye & Vision Sciences
Depositing User:	Symplectic Admin
Date Deposited:	10 Feb 2026 16:13
Last Modified:	28 Feb 2026 23:15
DOI:	10.1530/vb-25-0010
Open Access URL:	https://vb.bioscientifica.com/view/journals/vb/aop...
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3196957
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