{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:08:15Z","timestamp":1786133295691,"version":"build-2736575974"},"reference-count":107,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Nierstichting","doi-asserted-by":"crossref","award":["19OP012"],"award-info":[{"award-number":["19OP012"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018694","name":"HORIZON EUROPE Marie Sklodowska-Curie Actions","doi-asserted-by":"crossref","award":["860977"],"award-info":[{"award-number":["860977"]}],"id":[{"id":"10.13039\/100018694","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2026,4]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n Myofibroblasts and injury repair\u2013related cell types were exclusively observed in polycystic kidney disease and enriched within the cyst microenvironment.<\/jats:p>\n <\/jats:list-item>\n \n Cyst-associated gene signature of 45 genes with decreased expression further away from the cysts was largely related to inflammation.<\/jats:p>\n <\/jats:list-item>\n \n Communication in low-inflamed cystic microdomains related to cellular signaling, morphogenesis, and inflammation in polycystic kidney disease.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Changes in the cyst microenvironment in polycystic kidney disease (PKD) may drive progressive cyst formation. Bulk-cell and single-cell RNA sequencing have advanced our understanding of altered signaling; however, the lack of spatial information has limited our insights into local gene expression and cellular communication near cysts.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We used wild-type and\n Pkd1<\/jats:italic>\n -deficient mouse kidneys to generate 10\u00d7 Genomics Visium Spatial Gene Expression datasets. Using our single-cell mouse kidney atlas and single-cell sequencing data for spot deconvolution, we enhanced resolution and estimated enriched cell types. We analyzed spatial gene expression patterns and used a cyst-centered analysis to identify cyst-associated gene signature. Cell communication near cysts was investigated, identifying key ligand-receptors. Prioritized key factors were validated in tissues.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We observed enrichment of fibroblasts, injury repair\u2013related cell types, and diverse immune populations in PKD. Injury repair\u2013related cells were exclusively observed in PKD, predominantly localized within immune cell\u2013dense regions near cysts. These cells collectively contributed to the altered gene expression profile in PKD, including cyst-associated signature genes related to inflammatory processes. Analysis of cellular communication in less-inflamed regions around cysts revealed the involvement of multiple cell types. Key ligand-receptor interactions were associated with cytokine signaling, fibrosis, cellular development, and repair. These included\n Angpt2<\/jats:italic>\n ,\n C3<\/jats:italic>\n ,\n Csf1<\/jats:italic>\n ,\n Cxcl12<\/jats:italic>\n ,\n Il34<\/jats:italic>\n ,\n Gas6<\/jats:italic>\n ,\n Il16<\/jats:italic>\n ,\n Mdk<\/jats:italic>\n ,\n Mif<\/jats:italic>\n ,\n Ptn<\/jats:italic>\n ,\n Sfrp2<\/jats:italic>\n ,\n Spp1<\/jats:italic>\n ,\n Sdc1<\/jats:italic>\n ,\n Tnc<\/jats:italic>\n ,\n Tnfsf12<\/jats:italic>\n , and\n Wnt5a<\/jats:italic>\n . In addition, extracellular matrix (ECM) proteins implicated in immune response, ECM remodeling, cell adhesion, and cell signaling were identified, such as\n Adam9<\/jats:italic>\n ,\n Adam10<\/jats:italic>\n ,\n Col1a1, Col3a1, Col4a2, Lamb2, Lamc1, Efnb1<\/jats:italic>\n ,\n Efnb2<\/jats:italic>\n ,\n Thbs1, Thbs2<\/jats:italic>\n , and\n Vcam1<\/jats:italic>\n . Immunohistochemistry confirmed expression of Syndecan-1-Collagen IV, Midkine-Integrin\n \u03b2<\/jats:italic>\n 1, CSF-1, Pleiotrophin, and Tenascin-C in cystic kidneys.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Spatial transcriptomics in PKD revealed enrichment of (myo)fibroblasts, immune, and injury repair\u2013related cells near cysts, creating a (pro)inflammatory and (pro)fibrotic niche. Key ligand-receptor and ECM interactions were identified and validated.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000000894","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:01:03Z","timestamp":1760112063000},"page":"713-730","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Spatial Transcriptomics Reveals Injured Cells, Signature Genes, and Communication Patterns in the Cyst Microenvironment of Polycystic Kidney Disease"],"prefix":"10.1681","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7937-0992","authenticated-orcid":false,"given":"Sevtap A.","family":"Yasinoglu","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-6090","authenticated-orcid":false,"given":"Claudio","family":"Novella-Rausell","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9367-5730","authenticated-orcid":false,"given":"Lisanne E.","family":"Wisse","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6181-3983","authenticated-orcid":false,"given":"Kyra L.","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8601-2149","authenticated-orcid":false,"given":"Ahmed","family":"Mahfouz","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Delft Bioinformatics Lab, TU Delft, Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1214-500X","authenticated-orcid":false,"given":"Hans J.","family":"Baelde","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6974-7143","authenticated-orcid":false,"given":"Dorien J.M.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, The 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