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Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension

Portopulmonary hypertension (PoPH) is a type of pulmonary vascular disease due to portal hypertension that exhibits high morbidity and mortality. The mechanisms driving disease are unknown, and transcriptional characteristics unique to the PoPH liver remain unexplored. Here, we apply single nuclear...

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Autores principales: Jose, Arun, Elwing, Jean M., Kawut, Steven M., Pauciulo, Michael W., Sherman, Kenneth E., Nichols, William C., Fallon, Michael B., McCormack, Francis X.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10412637/
https://www.ncbi.nlm.nih.gov/pubmed/37558836
http://dx.doi.org/10.1038/s42003-023-05193-3
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author Jose, Arun
Elwing, Jean M.
Kawut, Steven M.
Pauciulo, Michael W.
Sherman, Kenneth E.
Nichols, William C.
Fallon, Michael B.
McCormack, Francis X.
author_facet Jose, Arun
Elwing, Jean M.
Kawut, Steven M.
Pauciulo, Michael W.
Sherman, Kenneth E.
Nichols, William C.
Fallon, Michael B.
McCormack, Francis X.
author_sort Jose, Arun
collection PubMed
description Portopulmonary hypertension (PoPH) is a type of pulmonary vascular disease due to portal hypertension that exhibits high morbidity and mortality. The mechanisms driving disease are unknown, and transcriptional characteristics unique to the PoPH liver remain unexplored. Here, we apply single nuclear RNA sequencing to compare cirrhotic livers from patients with and without PoPH. We identify characteristics unique to PoPH in cells surrounding the central hepatic vein, including increased growth differentiation factor signaling, enrichment of the arginine biosynthesis pathway, and differential expression of the bone morphogenic protein type II receptor and estrogen receptor type I genes. These results provide insight into the transcriptomic characteristics of the PoPH liver and mechanisms by which PoPH cellular dysfunction might contribute to pulmonary vascular remodeling.
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spelling pubmed-104126372023-08-11 Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension Jose, Arun Elwing, Jean M. Kawut, Steven M. Pauciulo, Michael W. Sherman, Kenneth E. Nichols, William C. Fallon, Michael B. McCormack, Francis X. Commun Biol Article Portopulmonary hypertension (PoPH) is a type of pulmonary vascular disease due to portal hypertension that exhibits high morbidity and mortality. The mechanisms driving disease are unknown, and transcriptional characteristics unique to the PoPH liver remain unexplored. Here, we apply single nuclear RNA sequencing to compare cirrhotic livers from patients with and without PoPH. We identify characteristics unique to PoPH in cells surrounding the central hepatic vein, including increased growth differentiation factor signaling, enrichment of the arginine biosynthesis pathway, and differential expression of the bone morphogenic protein type II receptor and estrogen receptor type I genes. These results provide insight into the transcriptomic characteristics of the PoPH liver and mechanisms by which PoPH cellular dysfunction might contribute to pulmonary vascular remodeling. Nature Publishing Group UK 2023-08-09 /pmc/articles/PMC10412637/ /pubmed/37558836 http://dx.doi.org/10.1038/s42003-023-05193-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jose, Arun
Elwing, Jean M.
Kawut, Steven M.
Pauciulo, Michael W.
Sherman, Kenneth E.
Nichols, William C.
Fallon, Michael B.
McCormack, Francis X.
Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension
title Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension
title_full Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension
title_fullStr Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension
title_full_unstemmed Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension
title_short Human liver single nuclear RNA sequencing implicates BMPR2, GDF15, arginine, and estrogen in portopulmonary hypertension
title_sort human liver single nuclear rna sequencing implicates bmpr2, gdf15, arginine, and estrogen in portopulmonary hypertension
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10412637/
https://www.ncbi.nlm.nih.gov/pubmed/37558836
http://dx.doi.org/10.1038/s42003-023-05193-3
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