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  1. Article: Commentary: Ghrelin promotes midbrain neural stem cells differentiation to dopaminergic neurons through the Wnt/β-catenin pathway.

    Gayden, Jenesis D / Freyberg, Zachary

    Frontiers in cellular neuroscience

    2020  Volume 14, Page(s) 248

    Language English
    Publishing date 2020-08-21
    Publishing country Switzerland
    Document type Journal Article ; Comment
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2020.00248
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A Spatial Atlas of Wnt Receptors in Adult Mouse Liver.

    Gayden, Jenesis / Hu, Shikai / Joseph, Paul N / Delgado, Evan / Liu, Silvia / Bell, Aaron / Puig, Stephanie / Monga, Satdarshan P / Freyberg, Zachary

    The American journal of pathology

    2023  Volume 193, Issue 5, Page(s) 558–566

    Abstract: Hepatic zonation is critical for most metabolic functions in liver. Wnt signaling plays an important role in establishing and maintaining liver zonation. Yet, the anatomic expression of Wnt signaling components, especially all 10 Frizzled (Fzd) receptors, ...

    Abstract Hepatic zonation is critical for most metabolic functions in liver. Wnt signaling plays an important role in establishing and maintaining liver zonation. Yet, the anatomic expression of Wnt signaling components, especially all 10 Frizzled (Fzd) receptors, has not been characterized in adult liver. To address this, the spatial expression of Fzd receptors was quantitatively mapped in adult mouse liver via multiplex fluorescent in situ hybridization. Although all 10 Fzd receptors were expressed within a metabolic unit, Fzd receptors 1, 4, and 6 were the highest expressed. Although most Wnt signaling occurs in zone 3, expression of most Fzd receptors was not zonated. In contrast, Fzd receptor 6 was preferentially expressed in zone 1. Wnt2 and Wnt9b expression was highly zonated and primarily found in zone 3. Therefore, the current results suggest that zonated Wnt/β-catenin signaling at baseline occurs primarily due to Wnt2 and Wnt9b rather than zonation of Fzd mRNA expression. Finally, the study showed that Fzd receptors and Wnts are not uniformly expressed by all hepatic cell types. Instead, there is broad distribution among both hepatocytes and nonparenchymal cells, including endothelial cells. Overall, this establishment of a definitive mRNA expression atlas, especially of Fzd receptors, opens the door to future functional characterization in healthy and diseased liver states.
    MeSH term(s) Mice ; Animals ; Receptors, Wnt/genetics ; Receptors, Wnt/metabolism ; Wnt Proteins/genetics ; In Situ Hybridization, Fluorescence ; Endothelial Cells/metabolism ; Frizzled Receptors/genetics ; Frizzled Receptors/metabolism ; Liver/metabolism ; Wnt Signaling Pathway ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; beta Catenin/metabolism
    Chemical Substances Receptors, Wnt ; Wnt Proteins ; Frizzled Receptors ; RNA, Messenger ; beta Catenin
    Language English
    Publishing date 2023-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2023.01.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Integrative multi-dimensional characterization of striatal projection neuron heterogeneity in adult brain.

    Gayden, Jenesis / Puig, Stephanie / Srinivasan, Chaitanya / Phan, BaDoi N / Abdelhady, Ghada / Buck, Silas A / Gamble, Mackenzie C / Tejeda, Hugo A / Dong, Yan / Pfenning, Andreas R / Logan, Ryan W / Freyberg, Zachary

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Striatal projection neurons (SPNs) are traditionally segregated into two subpopulations expressing dopamine (DA) ... ...

    Abstract Striatal projection neurons (SPNs) are traditionally segregated into two subpopulations expressing dopamine (DA) D
    Language English
    Publishing date 2023-10-21
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.04.539488
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Hepatic Stellate Cell-Specific Platelet-Derived Growth Factor Receptor-α Loss Reduces Fibrosis and Promotes Repair after Hepatocellular Injury.

    Kikuchi, Alexander / Singh, Sucha / Poddar, Minakshi / Nakao, Toshimasa / Schmidt, Heidi Marie / Gayden, Jenesis D / Sato, Toshifumi / Arteel, Gavin E / Monga, Satdarshan P

    The American journal of pathology

    2020  Volume 190, Issue 10, Page(s) 2080–2094

    Abstract: Platelet-derived growth factor receptor (PDGFR)-α plays roles in cell survival, proliferation, and differentiation; however, its function in chronic liver injury sequelae, such as fibrosis, is unknown. Hepatic stellate cells (HSCs), the primary mediators ...

    Abstract Platelet-derived growth factor receptor (PDGFR)-α plays roles in cell survival, proliferation, and differentiation; however, its function in chronic liver injury sequelae, such as fibrosis, is unknown. Hepatic stellate cells (HSCs), the primary mediators of fibrosis, undergo activation, which entails differentiation to myofibroblasts, proliferation, migration, and collagen deposition, partially in response to PDGFs. To examine the role of PDGFR-α in HSCs, Lrat-Cre recombinase and Pdgfra-floxed mice were bred to generate Lrat-CrePdgfra-/- (knockout) animals, which were subjected to chronic liver injury through carbon tetrachloride treatment, bile duct ligation, and 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Although no major difference was observed after other types of liver injury, PDGFR-α loss in HSCs led to a significant albeit transient reduction in fibrosis after carbon tetrachloride injury, associated with increased HSC death and reduced migration. There was continued alleviation of hepatocellular injury in knockout mice despite ongoing carbon tetrachloride insult, associated with increased numbers of CD68 and F480 macrophages and increased clearance of damaged hepatocytes. Altogether our findings support a profibrotic role of PDGFR-α in HSCs during chronic liver injury in vivo via regulation of HSC survival and migration and affect the immune microenvironment, especially macrophages in clearing dying hepatocytes. Thus, our study provides a preclinical foundation for the future testing of therapeutic PDGFR-α inhibition in hepatic fibrosis, especially in combination with other therapies.
    MeSH term(s) Animals ; Carbon Tetrachloride/metabolism ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Cell Movement/physiology ; Hepatic Stellate Cells/metabolism ; Liver/metabolism ; Liver Cirrhosis/pathology ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Mice, Knockout ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptor, Platelet-Derived Growth Factor alpha/metabolism
    Chemical Substances Carbon Tetrachloride (CL2T97X0V0) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Receptor, Platelet-Derived Growth Factor alpha (EC 2.7.10.1)
    Language English
    Publishing date 2020-06-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2943-9
    ISSN 1525-2191 ; 0002-9440
    ISSN (online) 1525-2191
    ISSN 0002-9440
    DOI 10.1016/j.ajpath.2020.06.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: WNT7B Regulates Cholangiocyte Proliferation and Function During Murine Cholestasis.

    Kosar, Karis / Cornuet, Pamela / Singh, Sucha / Lee, Elizabeth / Liu, Silvia / Gayden, Jenesis / Sato, Toshifumi / Freyberg, Zachary / Arteel, Gavin / Nejak-Bowen, Kari

    Hepatology communications

    2021  Volume 5, Issue 12, Page(s) 2019–2034

    Abstract: We previously identified an up-regulation of specific Wnt proteins in the cholangiocyte compartment during cholestatic liver injury and found that mice lacking Wnt secretion from hepatocytes and cholangiocytes showed fewer proliferating cholangiocytes ... ...

    Abstract We previously identified an up-regulation of specific Wnt proteins in the cholangiocyte compartment during cholestatic liver injury and found that mice lacking Wnt secretion from hepatocytes and cholangiocytes showed fewer proliferating cholangiocytes and high mortality in response to a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet, a murine model of primary sclerosing cholangitis. In vitro studies demonstrated that Wnt7b, one of the Wnts up-regulated during cholestasis, induces proliferation of cholangiocytes in an autocrine manner and increases secretion of proinflammatory cytokines. We hypothesized that loss of Wnt7b may exacerbate some of the complications of cholangiopathies by decreasing the ability of bile ducts to induce repair. Wnt7b-flox mice were bred with Krt19-cre mice to deplete Wnt7b expression in only cholangiocytes (CC) or with albumin-Cre mice to delete Wnt7b expression in both hepatocytes and cholangiocytes (HC + CC). These mice were placed on a DDC diet for 1 month then killed for evaluation. Contrary to our expectations, we found that mice lacking Wnt7b from CC and HC + CC compartments had improved biliary injury, decreased cellular senescence, and lesser bile acid accumulation after DDC exposure compared to controls, along with decreased expression of inflammatory cytokines. Although Wnt7b knockout (KO) resulted in fewer proliferating cholangiocytes, CC and HC + CC KO mice on a DDC diet also had more hepatocytes expressing cholangiocyte markers compared to wild-type mice on a DDC diet, indicating that Wnt7b suppression promotes hepatocyte reprogramming. Conclusion: Wnt7b induces a proproliferative proinflammatory program in cholangiocytes, and its loss is compensated for by conversion of hepatocytes to a biliary phenotype during cholestatic injury.
    MeSH term(s) Animals ; Bile Acids and Salts/metabolism ; Bile Ducts/cytology ; Cell Proliferation/genetics ; Cellular Senescence/genetics ; Cholestasis/genetics ; Disease Models, Animal ; Hepatocytes/metabolism ; Mice ; Mice, Knockout ; Proto-Oncogene Proteins/deficiency ; Wnt Proteins/deficiency
    Chemical Substances Bile Acids and Salts ; Proto-Oncogene Proteins ; Wnt Proteins ; Wnt7b protein, mouse
    Language English
    Publishing date 2021-08-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2471-254X
    ISSN (online) 2471-254X
    DOI 10.1002/hep4.1784
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  6. Article ; Online: Blockade of Cell Volume Regulatory Protein NKCC1 Increases TMZ-Induced Glioma Apoptosis and Reduces Astrogliosis.

    Luo, Lanxin / Guan, Xiudong / Begum, Gulnaz / Ding, Dawei / Gayden, Jenesis / Hasan, Md Nabiul / Fiesler, Victoria M / Dodelson, Jacob / Kohanbash, Gary / Hu, Baoli / Amankulor, Nduka M / Jia, Wang / Castro, Maria G / Sun, Baoshan / Sun, Dandan

    Molecular cancer therapeutics

    2020  Volume 19, Issue 7, Page(s) 1550–1561

    Abstract: Glioma is one of the most common primary malignant tumors of the central nervous system accounting for approximately 40% of all intracranial tumors. Temozolomide is a conventional chemotherapy drug for adjuvant treatment of patients with high-risk ... ...

    Abstract Glioma is one of the most common primary malignant tumors of the central nervous system accounting for approximately 40% of all intracranial tumors. Temozolomide is a conventional chemotherapy drug for adjuvant treatment of patients with high-risk gliomas, including grade II to grade IV. Our bioinformatic analysis of The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets and immunoblotting assay show that
    Language English
    Publishing date 2020-05-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2063563-1
    ISSN 1538-8514 ; 1535-7163
    ISSN (online) 1538-8514
    ISSN 1535-7163
    DOI 10.1158/1535-7163.MCT-19-0910
    Database MEDical Literature Analysis and Retrieval System OnLINE

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