{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:11:02Z","timestamp":1779361862221,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["1 R61 HL154137-01A1"],"award-info":[{"award-number":["1 R61 HL154137-01A1"]}]},{"name":"National Institutes of Health","award":["1 R01 HL159436"],"award-info":[{"award-number":["1 R01 HL159436"]}]},{"name":"National Institutes of Health","award":["5T32GM008448-26"],"award-info":[{"award-number":["5T32GM008448-26"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Barth Syndrome, a rare X-linked disorder affecting 1:300,000 live births, results from defects in Tafazzin, an acyltransferase that remodels cardiolipin and is essential for mitochondrial respiration. Barth Syndrome patients develop cardiomyopathy, muscular hypotonia and cyclic neutropenia during childhood, rarely surviving to middle age. At present, no effective therapy exists, and downstream transcriptional effects of Tafazzin dysfunction are incompletely understood. To identify novel, cell-specific, pathological pathways that mediate heart dysfunction, we performed single-nucleus RNA-sequencing (snRNA-seq) on wild-type (WT) and Tafazzin-knockout (Taz-KO) mouse hearts. We determined differentially expressed genes (DEGs) and inferred predicted cell\u2013cell communication networks from these data. Surprisingly, DEGs were distributed heterogeneously across the cell types, with fibroblasts, cardiomyocytes, endothelial cells, macrophages, adipocytes and pericytes exhibiting the greatest number of DEGs between genotypes. One differentially expressed gene was detected for the lymphatic endothelial and mesothelial cell types, while no significant DEGs were found in the lymphocytes. A Gene Ontology (GO) analysis of these DEGs showed cell-specific effects on biological processes such as fatty acid metabolism in adipocytes and cardiomyocytes, increased translation in cardiomyocytes, endothelial cells and fibroblasts, in addition to other cell-specific processes. Analysis of ligand\u2013receptor pair expression, to infer intercellular communication patterns, revealed the strongest dysregulated communication involved adipocytes and cardiomyocytes. For the knockout hearts, there was a strong loss of ligand\u2013receptor pair expression involving adipocytes, and cardiomyocyte expression of ligand\u2013receptor pairs underwent reorganization. These findings suggest that adipocyte and cardiomyocyte mitochondria may be most sensitive to mitochondrial Tafazzin deficiency and that rescuing adipocyte mitochondrial dysfunction, in addition to cardiomyocyte mitochondrial dysfunction, may provide therapeutic benefit in Barth Syndrome patients.<\/jats:p>","DOI":"10.3390\/ijms241411594","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:47:38Z","timestamp":1689727658000},"page":"11594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Single Cell Transcriptomic Analysis in a Mouse Model of Barth Syndrome Reveals Cell-Specific Alterations in Gene Expression and Intercellular Communication"],"prefix":"10.3390","volume":"24","author":[{"given":"Gayani","family":"Perera","sequence":"first","affiliation":[{"name":"Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3402-8429","authenticated-orcid":false,"given":"Liam","family":"Power","sequence":"additional","affiliation":[{"name":"Medical Scientist Training Program, Tufts University School of Medicine, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5217-3347","authenticated-orcid":false,"given":"Amy","family":"Larson","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina J.","family":"Codden","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junya","family":"Awata","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4712-6500","authenticated-orcid":false,"given":"Rebecca","family":"Batorsky","sequence":"additional","affiliation":[{"name":"Data Intensive Studies Center, Tufts University, Medford, MA 02155, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Strathdee","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3065-8498","authenticated-orcid":false,"given":"Michael T.","family":"Chin","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1750-1172-8-23","article-title":"Barth Syndrome","volume":"8","author":"Clarke","year":"2013","journal-title":"Orphanet J. 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