Browsing by Author "Zheng, Deyou"

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    Author Correction: REST regulates the cell cycle for cardiac development and regeneration
    (Springer Nature, 2018-01-12) Zhang, Donghong; Wang, Yidong; Lu, Pengfei; Wang, Ping; Yuan, Xinchun; Yan, Jianyun; Cai, Chenleng; Chang, Ching-Pin; Zheng, Deyou; Wu, Bingruo; Zhou, Bin; Medicine, School of Medicine
    Despite the importance of cardiomyocyte proliferation in cardiac development and regeneration, the mechanisms that promote cardiomyocyte cell cycle remain incompletely understood. RE1 silencing transcription factor (REST) is a transcriptional repressor of neuronal genes. Here we show that REST also regulates the cardiomyocyte cell cycle. REST binds and represses the cell cycle inhibitor gene p21 and is required for mouse cardiac development and regeneration. Rest deletion de-represses p21 and inhibits the cardiomyocyte cell cycle and proliferation in embryonic or regenerating hearts. By contrast, REST overexpression in cultured cardiomyocytes represses p21 and increases proliferation. We further show that p21 knockout rescues cardiomyocyte cell cycle and proliferation defects resulting from Rest deletion. Our study reveals a REST-p21 regulatory axis as a mechanism for cell cycle progression in cardiomyocytes, which might be exploited therapeutically to enhance cardiac regeneration.
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    REST regulates the cell cycle for cardiac development and regeneration
    (Nature Publishing group, 2017-12-07) Zhang, Donghong; Wang, Yidong; Lu, Pengfei; Wang, Ping; Yuan, Xinchun; Yan, Jianyun; Cai, Chenleng; Chang, Ching-Pin; Zheng, Deyou; Wu, Bingruo; Zhou, Bin; Medicine, School of Medicine
    Despite the importance of cardiomyocyte proliferation in cardiac development and regeneration, the mechanisms that promote cardiomyocyte cell cycle remain incompletely understood. RE1 silencing transcription factor (REST) is a transcriptional repressor of neuronal genes. Here we show that REST also regulates the cardiomyocyte cell cycle. REST binds and represses the cell cycle inhibitor gene p21 and is required for mouse cardiac development and regeneration. Rest deletion de-represses p21 and inhibits the cardiomyocyte cell cycle and proliferation in embryonic or regenerating hearts. By contrast, REST overexpression in cultured cardiomyocytes represses p21 and increases proliferation. We further show that p21 knockout rescues cardiomyocyte cell cycle and proliferation defects resulting from Rest deletion. Our study reveals a REST-p21 regulatory axis as a mechanism for cell cycle progression in cardiomyocytes, which might be exploited therapeutically to enhance cardiac regeneration., The mechanisms regulating cardiomyocyte proliferation during development and cardiac regeneration are incompletely understood. The authors show that the transcription factor REST regulates cardiomyocyte proliferation by binding and repressing the cell cycle inhibitor p21.
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    Retraction Note: REST regulates the cell cycle for cardiac development and regeneration
    (Springer Nature, 2024-02-22) Zhang, Donghong; Wang, Yidong; Lu, Pengfei; Wang, Ping; Yuan, Xinchun; Yan, Jianyun; Cai, Chenleng; Chang, Ching-Pin; Zheng, Deyou; Wu, Bingruo; Zhou, Bin; Medicine, School of Medicine
    Retraction to: Nature Communications 10.1038/s41467-017-02210-y, published online 07 December 2017 The authors have retracted this article because of significant concerns regarding a number of figures presented in this work that question the integrity of the data. After publication, several concerns were raised about the figures in this article. Specifically, * There appears to be a partial overlap between two panels of Figure 4e (bottom left corner for p21KO and top right for DKO). * There appears to be an overlap between a control panel from figure 2k and Rest imKO in Figure 5g (PH3 staining). * There appears to be image reuse between two samples in Figure 5g in the Aurora B staining row for Rest imKO and p21KO. * There appears to be an overlap between Figure 6f Ph3 staining for the Rest cDNA sample and Supplementary Fig. 6e, EdU staining, Rest cDNA, with fewer arrows and less visible DAPI staining. All authors agree with this retraction.
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    Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm
    (Springer Nature, 2021-11-17) Nomaru, Hiroko; Liu, Yang; De Bono, Christopher; Righelli, Dario; Cirino, Andrea; Wang, Wei; Song, Hansoo; Racedo, Silvia E.; Dantas, Anelisa G.; Zhang, Lu; Cai, Chen-Leng; Angelini, Claudia; Christiaen, Lionel; Kelly, Robert G.; Baldini, Antonio; Zheng, Deyou; Morrow, Bernice E.; Pediatrics, School of Medicine
    The poles of the heart and branchiomeric muscles of the face and neck are formed from the cardiopharyngeal mesoderm within the pharyngeal apparatus. They are disrupted in patients with 22q11.2 deletion syndrome, due to haploinsufficiency of TBX1, encoding a T-box transcription factor. Here, using single cell RNA-sequencing, we now identify a multilineage primed population within the cardiopharyngeal mesoderm, marked by Tbx1, which has bipotent properties to form cardiac and branchiomeric muscle cells. The multilineage primed cells are localized within the nascent mesoderm of the caudal lateral pharyngeal apparatus and provide a continuous source of cardiopharyngeal mesoderm progenitors. Tbx1 regulates the maturation of multilineage primed progenitor cells to cardiopharyngeal mesoderm derivatives while restricting ectopic non-mesodermal gene expression. We further show that TBX1 confers this balance of gene expression by direct and indirect regulation of enriched genes in multilineage primed progenitors and downstream pathways, partly through altering chromatin accessibility, the perturbation of which can lead to congenital defects in individuals with 22q11.2 deletion syndrome.
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    VISTA Emerges as a Promising Target against Immune Evasion Mechanisms in Medulloblastoma
    (MDPI, 2024-07-24) Muñoz Perez, Natalia; Pensabene, Juliana M.; Galbo, Phillip M., Jr.; Sadeghipour, Negar; Xiu, Joanne; Moziak, Kirsten; Yazejian, Rita M.; Welch, Rachel L.; Bell, W. Robert; Sengupta, Soma; Aulakh, Sonikpreet; Eberhart, Charles G.; Loeb, David M.; Eskandar, Emad; Zheng, Deyou; Zang, Xingxing; Martin, Allison M.; Pathology and Laboratory Medicine, School of Medicine
    Background: Relapsed medulloblastoma (MB) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment. Immune checkpoint inhibitors (ICIs) have struggled to mitigate this challenge, largely due to low T-cell infiltration and minimal PD-L1 expression. Identifying the mechanisms driving low T-cell infiltration is crucial for developing more effective immunotherapies. Methods: We utilize a syngeneic mouse model to investigate the tumor immune microenvironment of MB and compare our findings to transcriptomic and proteomic data from human MB. Results: Flow cytometry reveals a notable presence of CD45hi/CD11bhi macrophage-like and CD45int/CD11bint microglia-like tumor-associated macrophages (TAMs), alongside regulatory T-cells (Tregs), expressing high levels of the inhibitory checkpoint molecule VISTA. Compared to sham control mice, the CD45hi/CD11bhi compartment significantly expands in tumor-bearing mice and exhibits a myeloid-specific signature composed of VISTA, CD80, PD-L1, CTLA-4, MHCII, CD40, and CD68. These findings are corroborated by proteomic and transcriptomic analyses of human MB samples. Immunohistochemistry highlights an abundance of VISTA-expressing myeloid cells clustering at the tumor-cerebellar border, while T-cells are scarce and express FOXP3. Additionally, tumor cells exhibit immunosuppressive properties, inhibiting CD4 T-cell proliferation in vitro. Identification of VISTA's binding partner, VSIG8, on tumor cells, and its correlation with increased VISTA expression in human transcriptomic analyses suggests a potential therapeutic target. Conclusions: This study underscores the multifaceted mechanisms of immune evasion in MB and highlights the therapeutic potential of targeting the VISTA-VSIG axis to enhance anti-tumor responses.