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Updated: Mar 3, 2026
Isolation of CD146+ Resident Lung Mesenchymal Stromal Cells from Rat Lungs
Published on: June 17, 2016
Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular
Christa F Gaskill1, Erica J Carrier1, Jonathan A Kropski1
1Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine or Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee USA.
Abstract:
Pulmonary vascular disease is characterized by remodeling and loss of microvessels and is typically attributed to pathological responses in vascular endothelium or abnormal smooth muscle cell phenotypes. We have challenged this understanding by defining an adult pulmonary mesenchymal progenitor cell (MPC) that regulates both microvascular function and angiogenesis. The current understanding of adult MPCs and their roles in homeostasis versus disease has been limited by a lack of genetic markers with which to lineage label multipotent mesenchyme and trace the differentiation of these MPCs into vascular lineages. Here, we have shown that lineage-labeled lung MPCs expressing the ATP-binding cassette protein ABCG2 (ABCG2+) are pericyte progenitors that participate in microvascular homeostasis as well as adaptive angiogenesis. Activation of Wnt/β-catenin signaling, either autonomously or downstream of decreased BMP receptor signaling, enhanced ABCG2+ MPC proliferation but suppressed MPC differentiation into a functional pericyte lineage. Thus, enhanced Wnt/β-catenin signaling in ABCG2+ MPCs drives a phenotype of persistent microvascular dysfunction, abnormal angiogenesis, and subsequent exacerbation of bleomycin-induced fibrosis. ABCG2+ MPCs may, therefore, account in part for the aberrant microvessel function and remodeling that are associated with chronic lung diseases.
Insights
Adult lung mesenchymal progenitor cells (MPCs) expressing ABCG2 regulate microvessels. Aberrant Wnt/β-catenin signaling in these cells drives lung disease by impairing microvascular function and repair.
Area of Science:
- Pulmonary vascular biology
- Mesenchymal stem cell research
- Regenerative medicine
Background:
- Pulmonary vascular disease involves microvessel changes, traditionally linked to endothelium or smooth muscle cells.
- Adult pulmonary mesenchymal progenitor cells (MPCs) role in microvascular homeostasis and angiogenesis is poorly understood due to lack of lineage-tracing markers.
Purpose of the Study:
- To identify and characterize adult pulmonary mesenchymal progenitor cells (MPCs) involved in microvascular regulation.
- To investigate the role of ABCG2+ MPCs in lung microvascular homeostasis and angiogenesis.
- To determine the impact of Wnt/β-catenin signaling on ABCG2+ MPC function and its contribution to lung disease.
Main Methods:
- Lineage tracing using genetic markers to identify and track pulmonary mesenchymal progenitor cells (MPCs).
- Analysis of ABCG2+ MPCs in microvascular homeostasis and adaptive angiogenesis.
- Investigating the effects of Wnt/β-catenin signaling modulation on MPC proliferation and differentiation.
- Evaluating the role of ABCG2+ MPCs in bleomycin-induced lung fibrosis models.
Main Results:
- Lineage-labeled lung MPCs expressing ABCG2 (ABCG2+) were identified as pericyte progenitors crucial for microvascular homeostasis and angiogenesis.
- Activation of Wnt/β-catenin signaling promoted ABCG2+ MPC proliferation but inhibited their differentiation into functional pericytes.
- Enhanced Wnt/β-catenin signaling in ABCG2+ MPCs led to persistent microvascular dysfunction, aberrant angiogenesis, and worsened bleomycin-induced lung fibrosis.
Conclusions:
- ABCG2+ MPCs are key regulators of lung microvasculature and contribute to adaptive angiogenesis.
- Dysregulated Wnt/β-catenin signaling in ABCG2+ MPCs drives pathological microvascular remodeling and exacerbates lung fibrosis.
- These findings suggest ABCG2+ MPCs play a significant role in the aberrant microvessel function observed in chronic lung diseases.
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