{"entity": "researcher", "timestamp": "2026-09-26T23:30:42.664Z", "family": "Uhl\u00e9n", "given": "Per", "initials": "P", "orcid": "0000-0003-1446-1062", "affiliations": ["Laboratory for Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solnav\u00e4gen 9, 17177, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ad7d29180614f89800a512887eeedd1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ad7d29180614f89800a512887eeedd1"}}, "publications": [{"entity": "publication", "iuid": "feb4614735cd4d0089a1061d74a75fb1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/feb4614735cd4d0089a1061d74a75fb1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/feb4614735cd4d0089a1061d74a75fb1"}}, "title": "Ca2+ signal dynamics in maturing ureteric bud- and collecting duct-derived organoid tubules.", "authors": [{"family": "Carrisoza-Gayt\u00e1n", "given": "Rolando", "initials": "R", "orcid": "0000-0001-8771-9269", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8ba3c6c1f12f47b4bc5446ab47e6ce8f.json"}}, {"family": "Daily", "given": "Abigail", "initials": "A", "orcid": "0009-0005-0757-9873", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/81646b8449624cf9a0195f9a9b2bf7cd.json"}}, {"family": "Wolf", "given": "Kayla J", "initials": "KJ", "orcid": "0000-0001-6990-0283", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/227c1efdac424cb98d650f99e279d26a.json"}}, {"family": "Lasaad", "given": "Samia", "initials": "S", "orcid": "0009-0009-1101-2641", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b8218075b3694f8791cdede79213d1fb.json"}}, {"family": "Cantalupo", "given": "Anna", "initials": "A", "orcid": "0000-0002-5818-0900", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cca2a713f9a441c28770e1b1cdabba26.json"}}, {"family": "Nair", "given": "Pooja", "initials": "P", "orcid": "0009-0006-7077-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d09704607a5b46eb9b817d48ab735c33.json"}}, {"family": "van Gaal", "given": "Ronald C", "initials": "RC", "orcid": "0000-0002-4640-4612", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e1ce418bdab455291ca8adc6c7b6738.json"}}, {"family": "Uhl\u00e9n", "given": "Per", "initials": "P", "orcid": "0000-0003-1446-1062", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ad7d29180614f89800a512887eeedd1.json"}}, {"family": "Lewis", "given": "Jennifer A", "initials": "JA", "orcid": "0000-0002-0280-2774", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/125c21ce20fd4ef3a6b662f566ba7ace.json"}}, {"family": "Satlin", "given": "Lisa M", "initials": "LM", "orcid": "0000-0002-1744-1748", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f62ea2317ec24c80bb51ba3886e0ebdf.json"}}], "type": "journal article", "published": "2025-12-01", "journal": {"title": "Am. J. Physiol., Cell Physiol.", "issn": "1522-1563", "volume": "329", "issue": "6", "pages": "C1842-C1856", "issn-l": "0363-6143"}, "abstract": "Mechanical signals sensed by human stem cells are transduced via discrete signaling pathways to modulate developmental phenotype and function. Proximal tubules isolated from nephron lineage-derived kidney organoids undergo a developmental increase in abundance and/or activity of the basolateral mechanosensor PIEZO1 and Ca2+ signal transduction pathways (Carrisoza-Gaytan R, Kroll KT, Hiratsuka K, Gupta NR, Morizane R, Lewis JA, Satlin LM. Am J Physiol Cell Physiol 324: C757-C768, 2023). Here, we investigate whether human induced pluripotent stem cell (iPSC)-derived ureteric bud (UB) and collecting duct (CD) organoid cells exhibit a similar developmental increase in PIEZO1 function. Comparison of cells in tubules microdissected from UB and CD organoids cultured for 34-35 days or 62-65 days showed 1) increased intracellular Ca2+ concentration ([Ca2+]i) response to basolateral application of the selective PIEZO1 agonist Yoda1 and 2) decreased time to peak [Ca2+]i with advancing days in culture. Single-cell analyses of the Yoda1-induced [Ca2+]i response revealed 7- to 15-mHz [Ca2+]i oscillations that were more prevalent with advancing days in culture and differentiation (CD vs. UB). Concurrent exposure to inhibitors of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) or the plasma membrane Ca2+-ATPase (PMCA) dampened the amplitude of the Yoda1-induced [Ca2+]i oscillations. Bulk RNA analysis and pathway enrichment analysis revealed broad changes in genes associated with Ca2+ signaling, but not PIEZO1, with advancing days in culture and differentiation. These findings are consistent with a developmental increase in activity of PIEZO1 channels and/or maturation of associated pathways shaping Ca2+ signaling dynamics in maturing UB and CD organoids. Decoding of [Ca2+]i oscillations may identify molecular mechanisms important in morphological and functional differentiation of organoid tubules.NEW & NOTEWORTHY This investigation, focused on analyzing the role of PIEZO1 mechanotransduction in maturing human induced pluripotent stem cell (iPSC)-derived ureteric bud (UB) and collecting duct (CD) kidney organoids, unexpectedly reveals developmentally regulated Ca2+ oscillations and begins to dissect their mechanistic underpinnings. Specifically, transcriptomic analysis reveals that with time in culture and differentiation from UB to CD, organoids progressively acquire the molecular machinery necessary for complex Ca2+ signaling dynamics. These results lead us to speculate that information encoded in oscillatory signals drives renal epithelial differentiation.", "doi": "10.1152/ajpcell.00578.2025", "pmid": "41026830", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS2115211"}, {"db": "pmc", "key": "PMC12643228"}], "notes": [], "created": "2026-09-23T13:24:35.843Z", "modified": "2026-09-23T13:24:36.233Z"}, {"entity": "publication", "iuid": "ce84b8d00dc54c979945224e9cb43304", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ce84b8d00dc54c979945224e9cb43304.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ce84b8d00dc54c979945224e9cb43304"}}, "title": "Mending Fences: Na,K-ATPase signaling via Ca2+ in the maintenance of epithelium integrity.", "authors": [{"family": "Aperia", "given": "Anita", "initials": "A"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/04321d9fb805493db538489927a42c8f.json"}}, {"family": "Uhl\u00e9n", "given": "Per", "initials": "P", "orcid": "0000-0003-1446-1062", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ad7d29180614f89800a512887eeedd1.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "Cell Calcium", "issn": "1532-1991", "volume": "88", "pages": "102210", "issn-l": null}, "abstract": "Na,K-ATPase is a ubiquitous multifunctional protein that acts both as an ion pump and as a signal transducer. The signaling function is activated by ouabain in non-toxic concentrations. In epithelial cells the ouabain-bound Na,K-ATPase connects with the inositol 1,4,5-trisphosphate receptor via a short linear motif to activate low frequency Ca2+ oscillations. Within a couple of minutes this ouabain mediated signal has resulted in phosphorylation or dephosphorylation of 2580 phospho-sites. Proteins that control cell proliferation and cell adhesion and calmodulin regulated proteins are enriched among the ouabain phosphor-regulated proteins. The inositol 1,4,5-trisphosphate receptor and the stromal interaction molecule, which are both essential for the initiation of Ca2+ oscillations, belong to the ouabain phosphor-regulated proteins. Downstream effects of the ouabain-evoked Ca2+ signal in epithelial cells include interference with the intrinsic mitochondrial apoptotic process and stimulation of embryonic growth processes. The dual function of Na,K-ATPase as an ion pump and a signal transducer is now well established and evaluation of the physiological and pathophysiological consequences of this universal signal emerges as an urgent topic for future studies.", "doi": "10.1016/j.ceca.2020.102210", "pmid": "32380435", "labels": [], "xrefs": [{"db": "pii", "key": "S0143-4160(20)30052-X"}], "notes": [], "created": "2026-09-23T11:58:15.248Z", "modified": "2026-09-23T14:51:55.244Z"}, {"entity": "publication", "iuid": "580e442cf10f4a459619b385bbe3dd12", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/580e442cf10f4a459619b385bbe3dd12.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/580e442cf10f4a459619b385bbe3dd12"}}, "title": "Volumetric imaging: a potential tool to stage upper tract urothelial carcinoma.", "authors": [{"family": "Grahn", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-8048-9058", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0bc646e7a3254639afe2a7bb1d78f444.json"}}, {"family": "Tanaka", "given": "Nobuyuki", "initials": "N", "orcid": "0000-0003-0841-9167", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/764447a2897d46afb2f96fddeb3e6dee.json"}}, {"family": "Uhl\u00e9n", "given": "Per", "initials": "P", "orcid": "0000-0003-1446-1062", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ad7d29180614f89800a512887eeedd1.json"}}, {"family": "Brehmer", "given": "Marianne", "initials": "M", "orcid": "0000-0001-9232-363X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a0f84fc5cbaa41da809815756a5ae21d.json"}}], "type": "journal article", "published": "2019-11-00", "journal": {"title": "World J Urol", "issn": "1433-8726", "volume": "37", "issue": "11", "pages": "2297-2302", "issn-l": null}, "abstract": "To investigate whether volumetric imaging of tumor vasculature can be used to phenotypically characterize advanced upper tract urothelial carcinoma, and if this technique can distinguish aggressive invasive tumors from non-aggressive superficial ones.\n\nIn a pilot study, two TaG1 and two T3G3 formalin-fixed paraffin-embedded (FFPE) tumor samples were examined using the DIPCO pipeline (Tanaka et al. in Nature Biomed Eng 1(10):796-806. https://doi.org/10.1038/s41551-017-0139-0 , 2017). Briefly, punch biopsies of FFPE tumors were deparaffinized, cleared, immunolabeled with the vessel marker CD34 and imaged with a light-sheet microscope. Thereafter, the three-dimensional (3D) vasculature of the tumors was analyzed and characterized using a specialized image processing software.\n\nWe found that T3G3 tumors had increased CD34 density kurtosis and skewness compared to TaG1 tumors. This suggests that analysis of the 3D vasculature can distinguish between high-grade invasive and low-grade superficial tumors.\n\nVolumetric imaging of tumor samples may represent novel methodology that can complement conventional histopathology. Volumetric imaging enabled us to differentiate between invasive and non-invasive upper tract urothelial carcinoma. The method is of particular interest in diagnostic work-up of patients with upper tract urothelial carcinoma as previous findings indicate that volumetric imaging of vascular patterns could be used to differentiate superficial and invasive urothelial carcinoma, irrespective of if the tumor sample was deep or superficial. However, further and more extensive studies are required before this method can be applied clinically.", "doi": "10.1007/s00345-019-02682-1", "pmid": "30820651", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6825635"}, {"db": "pii", "key": "10.1007/s00345-019-02682-1"}], "notes": [], "created": "2026-09-23T13:30:35.511Z", "modified": "2026-09-23T13:30:35.678Z"}, {"entity": "publication", "iuid": "d9cfed0672fc4390919986809cb2ce7c", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d9cfed0672fc4390919986809cb2ce7c.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d9cfed0672fc4390919986809cb2ce7c"}}, "title": "A Zeb2-miR-200c loop controls midbrain dopaminergic neuron neurogenesis and migration.", "authors": [{"family": "Yang", "given": "Shanzheng", "initials": "S", "orcid": "0000-0002-5624-0818", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b6c791e551124310b218ce55b3d4f2fb.json"}}, {"family": "Toledo", "given": "Enrique M", "initials": "EM", "orcid": "0000-0002-1460-4708", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3e597210434a40b3bce183cb88284295.json"}}, {"family": "Rosmaninho", "given": "Pedro", "initials": "P"}, {"family": "Peng", "given": "Changgeng", "initials": "C"}, {"family": "Uhl\u00e9n", "given": "Per", "initials": "P", "orcid": "0000-0003-1446-1062", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ad7d29180614f89800a512887eeedd1.json"}}, {"family": "Castro", "given": "Diogo S", "initials": "DS"}, {"family": "Arenas", "given": "Ernest", "initials": "E"}], "type": "journal article", "published": "2018-06-25", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "1", "pages": "75", "issn-l": "2399-3642"}, "abstract": "Zeb2 is a homeodomain transcription factor that plays pleiotropic functions during embryogenesis, but its role for midbrain dopaminergic (mDA) neuron development is unknown. Here we report that Zeb2 is highly expressed in progenitor cells in the ventricular zone of the midbrain floor plate and downregulated in postmitotic neuroblasts. Functional experiments show that Zeb2 expression in the embryonic ventral midbrain is dynamically regulated by a negative feedback loop that involves miR-200c. We also find that Zeb2 overexpression reduces the levels of CXCR4, NR4A2, and PITX3 in the developing ventral midbrain in vivo, resulting in migration and mDA differentiation defects. This phenotype was recapitulated by miR-200c knockdown, suggesting that the Zeb2-miR-200c loop prevents the premature differentiation of mDA progenitors into postmitotic cells and their migration. Together, our study establishes Zeb2 and miR-200c as critical regulators that maintain the balance between mDA progenitor proliferation and neurogenesis.", "doi": "10.1038/s42003-018-0080-0", "pmid": "30271956", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6123725"}, {"db": "pii", "key": "10.1038/s42003-018-0080-0"}], "notes": [], "created": "2026-09-23T11:53:44.507Z", "modified": "2026-09-23T11:53:44.681Z"}]}