Key genes and pathways of pulmonary hypertension identified by integrating bulk and single-cell RNA sequencing
Abstract
Pulmonary hypertension (PH) is a progressive vascular disease, yet the underlying cell-type-specific molecular networks and diagnostic biomarkers remain incompletely defined. Integrating single-cell and bulk transcriptomics, we identified 14 pulmonary cell types in PH, with smooth muscle cells (SMCs) as a central communication hub interacting with monocytes and macrophages. High-dimensional weighted gene co-expression network analysis (hdWGCNA) revealed 4 SMC modules enriched in extracellular matrix organization, TGF-β, and HIF-1 pathways. A five-gene diagnostic signature distinguished PH from controls with an area under the curve of 0.895. Immune infiltration and enrichment analysis showed that activated CD4 memory T cells, activated dendritic cells, and resting mast cells increased in the PH group, while angiogenesis and epithelial-mesenchymal transition pathway were upregulated. In hypoxic human pulmonary artery SMCs, milk fat globule-epidermal growth factor-8 (MFGE8), secreted frizzled-related protein 2 (SFRP2), S100 calcium-binding protein A11 (S100A11), and procollagen C-endopeptidase enhancer 2 (PCOLCE2) were upregulated, and their knockdown suppressed proliferation, highlighting them as potential biomarkers and drivers of vascular remodeling, revealing a new molecular mechanism for PH and providing insights for potential therapeutic targets.
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BibTeX
@article{wu2026genes,
title = {{Key genes and pathways of pulmonary hypertension identified by integrating bulk and single-cell RNA sequencing}},
author = {Peipei Wu and Jingru Huan and Chengliang Liu and Haiyang Jin and Ran Wang and Yong Wang and Cheng Cao and Binbin Zhang},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117846},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03227-X},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Key genes and pathways of pulmonary hypertension identified by integrating bulk and single-cell RNA sequencing
AU - Peipei Wu
AU - Jingru Huan
AU - Chengliang Liu
AU - Haiyang Jin
AU - Ran Wang
AU - Yong Wang
AU - Cheng Cao
AU - Binbin Zhang
PY - 2026
DA - 2026/10/12
JO - iScience
DO - 10.1016/j.isci.2026.117846
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03227-X
AB - Pulmonary hypertension (PH) is a progressive vascular disease, yet the underlying cell-type-specific molecular networks and diagnostic biomarkers remain incompletely defined. Integrating single-cell and bulk transcriptomics, we identified 14 pulmonary cell types in PH, with smooth muscle cells (SMCs) as a central communication hub interacting with monocytes and macrophages. High-dimensional weighted gene co-expression network analysis (hdWGCNA) revealed 4 SMC modules enriched in extracellular matrix organization, TGF-β, and HIF-1 pathways. A five-gene diagnostic signature distinguished PH from controls with an area under the curve of 0.895. Immune infiltration and enrichment analysis showed that activated CD4 memory T cells, activated dendritic cells, and resting mast cells increased in the PH group, while angiogenesis and epithelial-mesenchymal transition pathway were upregulated. In hypoxic human pulmonary artery SMCs, milk fat globule-epidermal growth factor-8 (MFGE8), secreted frizzled-related protein 2 (SFRP2), S100 calcium-binding protein A11 (S100A11), and procollagen C-endopeptidase enhancer 2 (PCOLCE2) were upregulated, and their knockdown suppressed proliferation, highlighting them as potential biomarkers and drivers of vascular remodeling, revealing a new molecular mechanism for PH and providing insights for potential therapeutic targets.
SN - 2589-0042
ER -