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  1. Article ; Online: Bicellular Localization of Tricellular Junctional Protein Angulin-3/ILDR2 Allows Detection of Podocyte Injury.

    Higashi, Atsuko Y / Saito, Akira C / Higashi, Tomohito / Furuse, Kyoko / Furuse, Mikio / Chiba, Hideki / Kazama, Junichiro J

    The American journal of pathology

    2024  Volume 194, Issue 5, Page(s) 673–683

    Abstract: Podocytes serve as part of the renal filtration unit with slit diaphragms. Although the structure of slit diaphragms between two cells is well characterized, how the tricellular contact of podocytes is organized and how it changes in injured podocytes ... ...

    Abstract Podocytes serve as part of the renal filtration unit with slit diaphragms. Although the structure of slit diaphragms between two cells is well characterized, how the tricellular contact of podocytes is organized and how it changes in injured podocytes remains unknown. This study focused on a tricellular junction protein, angulin-3, and its localization in healthy podocytes, in developmental stages, and in pathologic conditions, using a newly established monoclonal antibody. Angulin-3 was confined at tricellular junctions of primordial podocytes, then transiently localized at bicellular junctions as foot process interdigitation developed and the intercellular junctions rearranged into slit diaphragm, and eventually distributed in a sparse punctate pattern on the foot processes of adult podocytes. In the rodent podocyte injury models, angulin-3 showed bicellular localization between the foot processes, and the localization turned from punctate to dashed linear pattern along the effaced foot processes with the progression of podocyte injury. Angulin-3 also accumulated between foot processes in a linear pattern in kidney biopsy samples of human nephrotic syndrome. Additionally, the line length of angulin-3 staining signal correlated with risk of relapse under glucocorticoid therapy in patients with minimal change nephrotic syndrome. This study proposes an image program to score the linearity of the accumulation pattern of angulin-3 to evaluate the relapse risk of patients with minimal change nephrotic syndrome.
    MeSH term(s) Adult ; Humans ; Podocytes/metabolism ; Tight Junctions/pathology ; Nephrosis, Lipoid/metabolism ; Nephrosis, Lipoid/pathology ; Intercellular Junctions/metabolism ; Recurrence
    Language English
    Publishing date 2024-02-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2024.01.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: ZnUMBA - a live imaging method to detect local barrier breaches.

    Higashi, Tomohito / Stephenson, Rachel E / Schwayer, Cornelia / Huljev, Karla / Higashi, Atsuko Y / Heisenberg, Carl-Philipp / Chiba, Hideki / Miller, Ann L

    Journal of cell science

    2023  Volume 136, Issue 15

    Abstract: Epithelial barrier function is commonly analyzed using transepithelial electrical resistance, which measures ion flux across a monolayer, or by adding traceable macromolecules and monitoring their passage across the monolayer. Although these methods ... ...

    Abstract Epithelial barrier function is commonly analyzed using transepithelial electrical resistance, which measures ion flux across a monolayer, or by adding traceable macromolecules and monitoring their passage across the monolayer. Although these methods measure changes in global barrier function, they lack the sensitivity needed to detect local or transient barrier breaches, and they do not reveal the location of barrier leaks. Therefore, we previously developed a method that we named the zinc-based ultrasensitive microscopic barrier assay (ZnUMBA), which overcomes these limitations, allowing for detection of local tight junction leaks with high spatiotemporal resolution. Here, we present expanded applications for ZnUMBA. ZnUMBA can be used in Xenopus embryos to measure the dynamics of barrier restoration and actin accumulation following laser injury. ZnUMBA can also be effectively utilized in developing zebrafish embryos as well as cultured monolayers of Madin-Darby canine kidney (MDCK) II epithelial cells. ZnUMBA is a powerful and flexible method that, with minimal optimization, can be applied to multiple systems to measure dynamic changes in barrier function with spatiotemporal precision.
    MeSH term(s) Animals ; Dogs ; Epithelial Cells ; Zinc ; Zebrafish ; Madin Darby Canine Kidney Cells ; Tight Junctions ; Actins
    Chemical Substances Zinc (J41CSQ7QDS) ; Actins
    Language English
    Publishing date 2023-08-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.260668
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Claudin-9 constitutes tight junctions of folliculo-stellate cells in the anterior pituitary gland.

    Higashi, Atsuko Y / Higashi, Tomohito / Furuse, Kyoko / Ozeki, Kana / Furuse, Mikio / Chiba, Hideki

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 21642

    Abstract: The anterior pituitary gland regulates growth, metabolism, and reproduction by secreting hormones. Folliculo-stellate (FS) cells are non-endocrine cells located among hormone-producing cells in the anterior pituitary glands. They form follicular lumens, ... ...

    Abstract The anterior pituitary gland regulates growth, metabolism, and reproduction by secreting hormones. Folliculo-stellate (FS) cells are non-endocrine cells located among hormone-producing cells in the anterior pituitary glands. They form follicular lumens, which are sealed by tight junctions (TJs). Although FS cells are hypothesized to contribute to fine-tuning of endocrine cells, little is known about the exact roles of FS cells. Here, we investigated the molecular composition of TJs in FS cells. We demonstrated that occludin is a good marker for TJs in the pituitary gland and examined the structure of the lumens surrounded by FS cells. We also found that claudin-9 is a major component of TJs in the FS cells. In immunoelectron microscopy, claudin-9 was specifically localized at TJs of the FS cells. The expression of claudin-9 was gradually increased in the pituitary gland after birth, suggesting that claudin-9 is developmentally regulated and performs some specific functions on the paracellular barrier of follicles in the pituitary gland. Furthermore, we found that angulin-1, angulin-2, and tricellulin are localized at the tricellular contacts of the FS cells. Our findings provide a first comprehensive molecular profile of TJs in the FS cells, and may lead us towards unveiling the FS cell functions.
    MeSH term(s) Animals ; Astrocytes/metabolism ; Cell Physiological Phenomena ; Claudins/metabolism ; Claudins/physiology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Occludin/metabolism ; Pituitary Gland/metabolism ; Pituitary Gland, Anterior/cytology ; Pituitary Gland, Anterior/metabolism ; Pituitary Gland, Anterior/physiology ; Tight Junctions/metabolism ; Tight Junctions/physiology
    Chemical Substances Claudins ; Cldn9 protein, mouse ; Occludin
    Language English
    Publishing date 2021-11-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-01004-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Expression Profiling of Fibroblasts in Chronic and Acute Disease Models Reveals Novel Pathways in Kidney Fibrosis.

    Higashi, Atsuko Y / Aronow, Bruce J / Dressler, Gregory R

    Journal of the American Society of Nephrology : JASN

    2018  Volume 30, Issue 1, Page(s) 80–94

    Abstract: Background: Renal interstitial fibrosis results from activation and proliferation of fibroblasts to myofibroblasts, secretion and accumulation of extracellular matrix, and displacement of normal renal tubules. In contrast to chronic renal disease, acute ...

    Abstract Background: Renal interstitial fibrosis results from activation and proliferation of fibroblasts to myofibroblasts, secretion and accumulation of extracellular matrix, and displacement of normal renal tubules. In contrast to chronic renal disease, acute injury may be repaired, a process that includes a decrease in the number of myofibroblasts in the interstitium and degradation of the accumulated extracellular matrix, leaving little evidence of prior injury.
    Methods: To investigate whether activated fibroblasts demonstrate changes in gene expression that correspond with regression after acute injury but are not observed in chronic models of fibrosis, we used microarrays to analyze gene expression patterns among fibroblast populations at different stages of injury or repair. We then mined the data for signaling pathways in fibroblasts corresponding to the acute proliferative, regression, and chronic phases of renal injury.
    Results: We identified multiple gene clusters with changes that correlate with the three phases of renal injury, including changes in levels of receptors for the antifibrotic factor PGE2. In adult renal fibroblast cultures, PGE2 was able to upregulate many genes that are suppressed by the profibrotic cytokine TGF-
    Conclusions: Inherent gene expression changes in activated fibroblasts accompany the transition from AKI to repair and regeneration. In chronic models, however, activated fibroblasts are resistant to the antifibrotic effects of PGE2 due to suppression of a subset of PGE receptors.
    MeSH term(s) Acute Kidney Injury/genetics ; Acute Kidney Injury/pathology ; Animals ; Cell Differentiation/genetics ; Cells, Cultured ; Dinoprostone/pharmacology ; Disease Models, Animal ; Extracellular Matrix/metabolism ; Fibroblasts/cytology ; Fibrosis/genetics ; Fibrosis/pathology ; Gene Expression Profiling ; Gene Expression Regulation ; Immunohistochemistry ; Mice ; Myofibroblasts/cytology ; Real-Time Polymerase Chain Reaction/methods ; Renal Insufficiency, Chronic/genetics ; Renal Insufficiency, Chronic/pathology ; Signal Transduction/genetics
    Chemical Substances Dinoprostone (K7Q1JQR04M)
    Language English
    Publishing date 2018-12-13
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2018060644
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: EpCAM proteolysis and release of complexed claudin-7 repair and maintain the tight junction barrier.

    Higashi, Tomohito / Saito, Akira C / Fukazawa, Yugo / Furuse, Mikio / Higashi, Atsuko Y / Ono, Masahiro / Chiba, Hideki

    The Journal of cell biology

    2022  Volume 222, Issue 1

    Abstract: TJs maintain the epithelial barrier by regulating paracellular permeability. Since TJs are under dynamically fluctuating intercellular tension, cells must continuously survey and repair any damage. However, the underlying mechanisms allowing cells to ... ...

    Abstract TJs maintain the epithelial barrier by regulating paracellular permeability. Since TJs are under dynamically fluctuating intercellular tension, cells must continuously survey and repair any damage. However, the underlying mechanisms allowing cells to sense TJ damage and repair the barrier are not yet fully understood. Here, we showed that proteinases play an important role in the maintenance of the epithelial barrier. At TJ break sites, EpCAM-claudin-7 complexes on the basolateral membrane become accessible to apical membrane-anchored serine proteinases (MASPs) and the MASPs cleave EpCAM. Biochemical data and imaging analysis suggest that claudin-7 released from EpCAM contributes to the rapid repair of damaged TJs. Knockout (KO) of MASPs drastically reduced barrier function and live-imaging of TJ permeability showed that MASPs-KO cells exhibited increased size, duration, and frequency of leaks. Together, our results reveal a novel mechanism of TJ maintenance through the localized proteolysis of EpCAM at TJ leaks, and provide a better understanding of the dynamic regulation of epithelial permeability.
    MeSH term(s) Claudins/genetics ; Claudins/metabolism ; Epithelial Cell Adhesion Molecule/genetics ; Epithelial Cell Adhesion Molecule/metabolism ; Mannose-Binding Protein-Associated Serine Proteases/metabolism ; Proteolysis ; Tight Junctions/metabolism ; Gene Knockout Techniques
    Chemical Substances Claudins ; Epithelial Cell Adhesion Molecule ; Mannose-Binding Protein-Associated Serine Proteases (EC 3.4.21.-)
    Language English
    Publishing date 2022-11-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.202204079
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Occludin and tricellulin facilitate formation of anastomosing tight-junction strand network to improve barrier function.

    Saito, Akira C / Higashi, Tomohito / Fukazawa, Yugo / Otani, Tetsuhisa / Tauchi, Masashi / Higashi, Atsuko Y / Furuse, Mikio / Chiba, Hideki

    Molecular biology of the cell

    2021  Volume 32, Issue 8, Page(s) 722–738

    Abstract: Tight junctions (TJs) are composed of a claudin-based anastomosing network of TJ strands at which plasma membranes of adjacent epithelial cells are closely attached to regulate the paracellular permeability. Although the TJ proteins occludin and ... ...

    Abstract Tight junctions (TJs) are composed of a claudin-based anastomosing network of TJ strands at which plasma membranes of adjacent epithelial cells are closely attached to regulate the paracellular permeability. Although the TJ proteins occludin and tricellulin have been known to be incorporated in the TJ strand network, their molecular functions remain unknown. Here, we established tricellulin/occludin-double knockout (dKO) MDCK II cells using a genome editing technique and evaluated the structure and barrier function of these cells. In freeze-fracture replica electron microscopy, the TJ strands of tricellulin/occludin-dKO cells had fewer branches and were less anastomosed compared with the controls. The paracellular permeability of ions and small tracers was increased in the dKO cells. A single KO of tricellulin or occludin had limited effects on the morphology and permeability of TJs. Mathematical simulation using a simplified TJ strand network model predicted that reduced cross-links in TJ strands lead to increased permeability of ions and small macromolecules. Furthermore, overexpression of occludin increased the complexity of TJ strand network and strengthened barrier function. Taken together, our data suggest that tricellulin and occludin mediate the formation and/or stabilization of TJ-strand branching points and contribute to the maintenance of epithelial barrier integrity.
    MeSH term(s) Animals ; Cell Line ; Claudins/metabolism ; Dogs ; Epithelial Cells/metabolism ; HEK293 Cells ; Humans ; MARVEL Domain Containing 2 Protein/metabolism ; MARVEL Domain Containing 2 Protein/physiology ; Madin Darby Canine Kidney Cells ; Occludin/metabolism ; Occludin/physiology ; Tight Junctions/metabolism ; Tight Junctions/physiology
    Chemical Substances Claudins ; MARVEL Domain Containing 2 Protein ; MARVELD2 protein, human ; OCLN protein, human ; Occludin
    Language English
    Publishing date 2021-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E20-07-0464
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Claudin‑9 is a novel prognostic biomarker for endometrial cancer.

    Endo, Yuta / Sugimoto, Kotaro / Kobayashi, Makoto / Kobayashi, Yasuyuki / Kojima, Manabu / Furukawa, Shigenori / Soeda, Shu / Watanabe, Takafumi / Higashi, Atsuko Y / Higashi, Tomohito / Hashimoto, Yuko / Fujimori, Keiya / Chiba, Hideki

    International journal of oncology

    2022  Volume 61, Issue 5

    Abstract: The tight‑junction protein claudin‑9 (CLDN9) is barely distributed in normal adult tissues but is ectopically expressed in various cancer types. Although multiple databases indicated upregulation of CLDN9 in endometrial cancers at the mRNA level, its ... ...

    Abstract The tight‑junction protein claudin‑9 (CLDN9) is barely distributed in normal adult tissues but is ectopically expressed in various cancer types. Although multiple databases indicated upregulation of CLDN9 in endometrial cancers at the mRNA level, its protein expression and biological roles remain obscure. In the present study, the prognostic significance of CLDN9 expression in endometrial cancer was evaluated by immunohistochemical staining and semi‑quantification using formalin‑fixed paraffin‑embedded specimens obtained from 248 endometrial carcinoma cases. A total of 43 cases (17.3%) had high CLDN9 expression, whereas 205 cases (82.7%) exhibited low CLDN9 expression. The 5‑year disease‑specific survival rates in the high and low CLDN9 expression groups were 62.8 and 87.8% (P<0.001), respectively. In addition, multivariate analysis revealed that high CLDN9 expression was an independent prognostic factor (hazard ratio, 4.99; 95% CI, 1.96‑12.70; P<0.001). Furthermore, CLDN9 expression was significantly correlated with the expression of CLDN6 (P<0.001), which is the closest CLDN member to CLDN9 and a poor prognostic factor for endometrial carcinoma. The 5‑year disease‑specific survival rate of cases with CLDN6‑high/CLDN9‑high, CLDN6‑high/CLDN9‑low and CLDN6‑low/CLDN9‑high status was 30.0, 37.5 and 72.7%, respectively, whereas that of CLDN6‑low/CLDN9‑low was 89.8% (P=0.004). In conclusion, aberrant CLDN9 expression is a predictor of poor prognosis for endometrial cancer and may be utilized in combination with CLDN6 to achieve higher sensitivity.
    MeSH term(s) Biomarkers ; Claudins/genetics ; Claudins/metabolism ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/pathology ; Female ; Formaldehyde ; Humans ; Prognosis ; RNA, Messenger/metabolism
    Chemical Substances Biomarkers ; CLDN9 protein, human ; Claudins ; RNA, Messenger ; Formaldehyde (1HG84L3525)
    Language English
    Publishing date 2022-09-21
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 1154403-x
    ISSN 1791-2423 ; 1019-6439
    ISSN (online) 1791-2423
    ISSN 1019-6439
    DOI 10.3892/ijo.2022.5425
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  8. Article ; Online: Pax2 and Pax8 Proteins Regulate Urea Transporters and Aquaporins to Control Urine Concentration in the Adult Kidney.

    Laszczyk, Ann M / Higashi, Atsuko Y / Patel, Sanjeevkumar R / Johnson, Craig N / Soofi, Abdul / Abraham, Saji / Dressler, Gregory R

    Journal of the American Society of Nephrology : JASN

    2020  Volume 31, Issue 6, Page(s) 1212–1225

    Abstract: Background: As the glomerular filtrate passes through the nephron and into the renal medulla, electrolytes, water, and urea are reabsorbed through the concerted actions of solute carrier channels and aquaporins at various positions along the nephron and ...

    Abstract Background: As the glomerular filtrate passes through the nephron and into the renal medulla, electrolytes, water, and urea are reabsorbed through the concerted actions of solute carrier channels and aquaporins at various positions along the nephron and in the outer and inner medulla. Proliferating stem cells expressing the nuclear transcription factor Pax2 give rise to renal epithelial cells. Pax2 expression ends once the epithelial cells differentiate into mature proximal and distal tubules, whereas expression of the related Pax8 protein continues. The collecting tubules and renal medulla are derived from Pax2-positive ureteric bud epithelia that continue to express Pax2 and Pax8 in adult kidneys. Despite the crucial role of Pax2 in renal development, functions for Pax2 or Pax8 in adult renal epithelia have not been established.
    Methods: To examine the roles of Pax2 and Pax8 in the adult mouse kidney, we deleted either
    Results: Mice with induced deletions of both
    Conclusions: These data reveal novel functions for Pax proteins in adult renal epithelia that are essential for retaining water and concentrating urine.
    MeSH term(s) Animals ; Aquaporins/physiology ; Female ; HEK293 Cells ; Humans ; Kidney/physiology ; Kidney Concentrating Ability/physiology ; Male ; Membrane Transport Proteins/physiology ; Mice ; Osmoregulation ; PAX2 Transcription Factor/genetics ; PAX2 Transcription Factor/physiology ; PAX8 Transcription Factor/genetics ; PAX8 Transcription Factor/physiology ; Urea Transporters
    Chemical Substances Aquaporins ; Membrane Transport Proteins ; PAX2 Transcription Factor ; PAX8 Transcription Factor ; Pax2 protein, mouse ; Pax8 protein, mouse
    Language English
    Publishing date 2020-05-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2019090962
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: CLDN15 is a novel diagnostic marker for malignant pleural mesothelioma.

    Watanabe, Masayuki / Higashi, Tomohito / Ozeki, Kana / Higashi, Atsuko Y / Sugimoto, Kotaro / Mine, Hayato / Takagi, Hironori / Ozaki, Yuki / Muto, Satoshi / Okabe, Naoyuki / Matsumura, Yuki / Hasegawa, Takeo / Shio, Yutaka / Suzuki, Hiroyuki / Chiba, Hideki

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 12554

    Abstract: Malignant mesothelioma is a cancer with a poor survival rate. It is difficult to diagnose mesotheliomas because they show a variety of histological patterns similar to those of various other cancers. However, since currently used positive markers for ... ...

    Abstract Malignant mesothelioma is a cancer with a poor survival rate. It is difficult to diagnose mesotheliomas because they show a variety of histological patterns similar to those of various other cancers. However, since currently used positive markers for mesotheliomas may show false positives or false negatives, a novel mesothelial positive marker is required. In the present study, we screened 25 claudins and found that claudin-15 is expressed in the mesothelial cells. We made new rat anti-human claudin-15 (CLDN15) monoclonal antibodies that selectively recognize CLDN15, and investigated whether CLDN15 is a good positive marker for malignant pleural mesotheliomas (MPMs) using MPM tissue samples by immunohistochemistry and semi-quantification of the expression level using an immunoreactive score (IRS) method. Of 42 MPM samples, 83% were positive for CLDN15. The positive ratio was equal to or greater than other positive markers for MPMs including calretinin (81%), WT-1 (50%), and D2-40 (81%). In 50 lung adenocarcinoma sections, four cases were positive for CLDN15 and the specificity (92%) was comparable with other markers (90-100%). Notably, CLDN15 was rarely detected in 24 non-mesothelial tumors in the tissue microarray (12/327 cases). In conclusion, CLDN15 can be used in the clinical setting as a positive marker for MPM diagnosis.
    MeSH term(s) Adenocarcinoma of Lung/diagnosis ; Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/pathology ; Adult ; Aged ; Aged, 80 and over ; Animals ; Biomarkers, Tumor/genetics ; Calbindin 2/genetics ; Claudins/genetics ; Diagnosis, Differential ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mesothelioma, Malignant/diagnosis ; Mesothelioma, Malignant/genetics ; Mesothelioma, Malignant/pathology ; Middle Aged ; Rats ; WT1 Proteins/genetics
    Chemical Substances Biomarkers, Tumor ; CALB2 protein, human ; Calbindin 2 ; Claudins ; WT1 Proteins ; WT1 protein, human ; claudin 15
    Language English
    Publishing date 2021-06-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-91464-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: From Otic Induction to Hair Cell Production: Pax2

    Schaefer, Stacy A / Higashi, Atsuko Y / Loomis, Benjamin / Schrepfer, Thomas / Wan, Guoqiang / Corfas, Gabriel / Dressler, Gregory R / Duncan, Robert Keith

    Stem cells and development

    2018  Volume 27, Issue 4, Page(s) 237–251

    Abstract: Producing hair cells of the inner ear is the major goal of ongoing research that combines advances in developmental and stem cell biology. The recent advent of an inner ear organoid protocol-resulting in three-dimensional stem cell-derived tissues ... ...

    Abstract Producing hair cells of the inner ear is the major goal of ongoing research that combines advances in developmental and stem cell biology. The recent advent of an inner ear organoid protocol-resulting in three-dimensional stem cell-derived tissues resembling vestibular sensory epithelia-has sparked interest in applications such as regeneration, drug discovery, and disease modeling. In this study, we adapted this protocol for a novel mouse embryonic stem cell line with a fluorescent reporter for Pax2 expression. We used Pax2
    MeSH term(s) Animals ; Cell Differentiation/genetics ; Cell Line ; Ear, Inner/cytology ; Ear, Inner/growth & development ; Ear, Inner/metabolism ; Gene Expression Regulation, Developmental ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Hair Cells, Auditory/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Fluorescence ; Mouse Embryonic Stem Cells/cytology ; Mouse Embryonic Stem Cells/metabolism ; Organogenesis/genetics ; Organoids/cytology ; Organoids/metabolism ; PAX2 Transcription Factor/genetics ; PAX2 Transcription Factor/metabolism
    Chemical Substances PAX2 Transcription Factor ; Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2018-01-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2142214-X
    ISSN 1557-8534 ; 1547-3287
    ISSN (online) 1557-8534
    ISSN 1547-3287
    DOI 10.1089/scd.2017.0142
    Database MEDical Literature Analysis and Retrieval System OnLINE

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