{"entity": "researcher", "timestamp": "2026-09-27T16:17:48.521Z", "family": "Tsai", "given": "Chang-Ru", "initials": "CR", "orcid": "0000-0001-5672-1235", "affiliations": ["Department of Integrative Physiology (C.-R.T., J.S., F.G., M.A.H.S., J.F.M.), Baylor College of Medicine, Houston, TX."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca2c2d9bee5143ee9277f25c033f26ff.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca2c2d9bee5143ee9277f25c033f26ff"}}, "publications": [{"entity": "publication", "iuid": "0891ec40faef4202b7a42f07df24cbe3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0891ec40faef4202b7a42f07df24cbe3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0891ec40faef4202b7a42f07df24cbe3"}}, "title": "YAP-Induced Glycolysis Drives Fibroinflammation and Disrupts Fibroblast Fidelity.", "authors": [{"family": "Tsai", "given": "Chang-Ru", "initials": "CR", "orcid": "0000-0001-5672-1235", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca2c2d9bee5143ee9277f25c033f26ff.json"}}, {"family": "Liu", "given": "Lin", "initials": "L", "orcid": "0000-0002-0343-6286", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb27cefe33ff42b1888e2a1d56be4598.json"}}, {"family": "Zhao", "given": "Yi", "initials": "Y", "orcid": "0000-0003-0989-8825", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8d4d4411ff6241a88e0eb5f680682757.json"}}, {"family": "Kim", "given": "Jong H", "initials": "JH", "orcid": "0000-0002-4491-212X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/08c7a78b8a094d9e9f5ba298f882f6da.json"}}, {"family": "Czarnewski", "given": "Paulo", "initials": "P", "orcid": "0000-0001-8150-4021", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/501677a1262c438aa4077b205bb39a72.json"}}, {"family": "Li", "given": "Rich Gang", "initials": "RG", "orcid": "0000-0001-9661-8304", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4d76f0e61d0748a1b366cc4f1e653b4f.json"}}, {"family": "Meng", "given": "Fansen", "initials": "F"}, {"family": "Zheng", "given": "Mingjie", "initials": "M"}, {"family": "Steimle", "given": "Jeffrey", "initials": "J", "orcid": "0000-0002-1369-9661", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0fffdfdcca224e888969b0f35cd4e583.json"}}, {"family": "Zhao", "given": "Xiaolei", "initials": "X", "orcid": "0000-0002-4697-3874", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a06a4c2f622f45cf9cb1bd08b855f575.json"}}, {"family": "Grisanti", "given": "Francisco", "initials": "F"}, {"family": "Sun", "given": "Zheng", "initials": "Z", "orcid": "0000-0002-6858-0633", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bb22b81fa2b14b9b9a9732eef0b9bb7b.json"}}, {"family": "Wang", "given": "Jun", "initials": "J", "orcid": "0000-0001-6874-9331", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e5f176a6b2324925908ef5dae2eae6be.json"}}, {"family": "Samee", "given": "Md Abul Hassan", "initials": "MAH", "orcid": "0000-0002-7472-1156", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d5f2db0e15994f0f892d487cf5adf6b4.json"}}, {"family": "Li", "given": "Xiao", "initials": "X", "orcid": "0000-0001-8527-4438", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c269b02ee5fe4c02a96f796423ef2cca.json"}}, {"family": "Martin", "given": "James F", "initials": "JF", "orcid": "0000-0002-7842-9857", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c441b60800af461b8edb908c9bf69bd7.json"}}], "type": "journal article", "published": "2025-12-05", "journal": {"title": "Circ. Res.", "issn": "1524-4571", "volume": "137", "issue": "12", "pages": "1443-1458", "issn-l": "0009-7330"}, "abstract": "Separation of the pulmonic and systemic circulation is essential for terrestrial life, and mammals have evolved distinct cardiac chambers with specialized structures and functions. Transcriptomics profiling revealed cellular heterogeneity between heart chambers. However, the mechanisms underlying chamber-specific transcriptomic and metabolic differences-and their functional significance-remain poorly understood. The Hippo/YAP (yes-associated protein) pathway is a conserved signaling network that regulates diverse cellular processes. The Hippo kinases inhibit YAP in cardiac fibroblasts (CF) to restrict fibrosis and inflammation. Nonetheless, how YAP regulates the metabolic microenvironment during homeostasis and fibroinflammation remains unclear.\n\nWe investigated YAP and glycolysis activity in the 4 cardiac chambers by scoring the expression of YAP target genes and glycolysis genes in human single-nucleus RNA sequencing data. To compare glucose uptake between the left and right atria, we measured isotope-labeled glucose uptake in isolated mouse atria. To study the role of YAP in CFs, we inactivated the Hippo kinases, Lats1 and Lats2, in mouse CFs and performed metabolic studies, snRNA-seq, single-nucleus assay for transposase-accessible chromatin with sequencing, and spatial transcriptomics.\n\nMetabolic and sequencing approaches revealed that Hippo-deficient CFs activated glycolysis to promote fibroinflammation. Inhibition of glycolysis or lactate production suppressed Hippo-deficient CF-induced fibrosis. Elevated YAP activity disrupted fibroblast lineage fidelity by inducing an osteochondroprogenitor cell state. Blocking macrophage expansion pharmacologically reduced Hippo-deficient CF proliferation and fibrosis. Sequencing and functional studies showed that macrophages secreted IGF1 (insulin-like growth factor 1) to activate IGF1 signaling in Hippo-deficient CFs to increase cell proliferation and fibrosis.\n\nWe discovered that right atrial CFs are more glycolytic and have higher YAP activity than CFs in other heart chambers. YAP activation in CFs induces glycolysis to drive fibrosis. YAP disrupts fibroblast lineage fidelity, driving them to a SOX9 (SRY-box transcription factor 9)-expressing osteochondroprogenitor cell state. Mechanistically, YAP activates the secretion of CSF1 (colony-stimulating factor 1) to promote macrophage expansion. Blocking macrophage expansion reduces Hippo-deficient CF proliferation, osteochondroprogenitor differentiation, and fibrosis, revealing that macrophages signal reciprocally to regulate CF cell states. Genomic and functional studies revealed that the upregulated IGF1 receptor in Hippo-deficient CFs enables them to receive macrophage-secreted IGF1, thereby further enhancing CF proliferation and fibrosis.", "doi": "10.1161/CIRCRESAHA.125.326480", "pmid": "41165345", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS2118149"}, {"db": "pmc", "key": "PMC12965804"}], "notes": [], "created": "2026-09-23T09:12:31.075Z", "modified": "2026-09-23T09:12:31.650Z"}, {"entity": "publication", "iuid": "8b321f9058a24912a42b05e02947a108", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/8b321f9058a24912a42b05e02947a108.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/8b321f9058a24912a42b05e02947a108"}}, "title": "Hippo-deficient cardiac fibroblasts differentiate into osteochondroprogenitors.", "authors": [{"family": "Tsai", "given": "Chang-Ru", "initials": "CR", "orcid": "0000-0001-5672-1235", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca2c2d9bee5143ee9277f25c033f26ff.json"}}, {"family": "Kim", "given": "Jong", "initials": "J"}, {"family": "Li", "given": "Xiao", "initials": "X"}, {"family": "Czarnewski", "given": "Paulo", "initials": "P"}, {"family": "Li", "given": "Rich", "initials": "R"}, {"family": "Meng", "given": "Fansen", "initials": "F"}, {"family": "Zheng", "given": "Mingjie", "initials": "M"}, {"family": "Zhao", "given": "Xiaolei", "initials": "X"}, {"family": "Steimle", "given": "Jeffrey", "initials": "J"}, {"family": "Grisanti", "given": "Francisco", "initials": "F"}, {"family": "Wang", "given": "Jun", "initials": "J"}, {"family": "Samee", "given": "Md Abul Hassan", "initials": "MAH"}, {"family": "Martin", "given": "James", "initials": "J"}], "type": "preprint", "published": "2023-09-08", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null}, "abstract": "Cardiac fibrosis, a common pathophysiology associated with various heart diseases, occurs from the excess deposition of extracellular matrix (ECM) 1 . Cardiac fibroblasts (CFs) are the primary cells that produce, degrade, and remodel ECM during homeostasis and tissue repair 2 . Upon injury, CFs gain plasticity to differentiate into myofibroblasts 3 and adipocyte-like 4,5 and osteoblast-like 6 cells, promoting fibrosis and impairing heart function 7 . How CFs maintain their cell state during homeostasis and adapt plasticity upon injury are not well defined. Recent studies have shown that Hippo signalling in CFs regulates cardiac fibrosis and inflammation 8-11 . Here, we used single-nucleus RNA sequencing (snRNA-seq) and spatially resolved transcriptomic profiling (ST) to investigate how the cell state was altered in the absence of Hippo signaling and how Hippo-deficient CFs interact with macrophages during cardiac fibrosis. We found that Hippo-deficient CFs differentiate into osteochondroprogenitors (OCPs), suggesting that Hippo restricts CF plasticity. Furthermore, Hippo-deficient CFs colocalized with macrophages, suggesting their intercellular communications. Indeed, we identified several ligand-receptor pairs between the Hippo-deficient CFs and macrophages. Blocking the Hippo-deficient CF-induced CSF1 signaling abolished macrophage expansion. Interestingly, blocking macrophage expansion also reduced OCP differentiation of Hippo-deficient CFs, indicating that macrophages promote CF plasticity.", "doi": "10.1101/2023.09.06.556593", "pmid": "38529510", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10962739"}, {"db": "pii", "key": "2023.09.06.556593"}], "notes": [], "created": "2026-09-23T13:50:13.927Z", "modified": "2026-09-23T13:50:13.947Z"}]}