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Yongmin Li, Jingwen Li, He Liu, Yanlong Liu, Binbin Cui
Colorectal cancer, the third most common cancer in both men and women, has gradually increased in recent years. MYSM1has been investigated as a regulator of hematopoiesis and lymphocyte development in human. It has been reported that some tumor-related genes were modulated by MYSM1. However, its exact role in cancer development remains unclear. Herein, we aimed to examine the expression level of MYSM1 in tumor tissues and its correlation with clinicopathology and survivals of patients with colorectal cancer (CRC)...
2017: PloS One
Yu Liu, Heng Zhu, Xiao-Xia Jiang, Bin Zhang, Li Liao, Yuan-Lin Liu, Yi Zhang, Hu Chen, Ning Mao
OBJECTIVE: To aimed at the establishment of mouse stably knockout of MYSM1 mesenchymal stem cell(MSC) line C3H10T1/2, and to investigate its immunological capacity of MSC in vitro. METHODS: To establish the stably transfected MSC cell line by using CRISPR-Cas9 technology. Then the Flow cytometry, quantitative PCR and Western blot were employed to detect whether the MYSM1 have been knockout yet. Furthermore, the immune modulatory effect of MYSM1(-/-) MSC was tested by addition of MYSM1(-/-) MSC supernatant into spleen lymphocyte and Foxp3 culture...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
Ehsan Bahrami, Maximilian Witzel, Tomas Racek, Jacek Puchałka, Sebastian Hollizeck, Naschla Greif-Kohistani, Daniel Kotlarz, Hans-Peter Horny, Regina Feederle, Heinrich Schmidt, Roya Sherkat, Doris Steinemann, Gudrun Göhring, Brigitte Schlegelbeger, Michael H Albert, Waleed Al-Herz, Christoph Klein
BACKGROUND: Myb-like, SWIRM, and MPN domains 1 (MYSM1) is a transcriptional regulator mediating histone deubiquitination. Its role in human immunity and hematopoiesis is poorly understood. OBJECTIVES: We sought to investigate the clinical, cellular, and molecular features in 2 siblings presenting with progressive bone marrow failure (BMF), immunodeficiency, and developmental aberrations. METHODS: We performed genome-wide homozygosity mapping, whole-exome and Sanger sequencing, immunophenotyping studies, and analysis of genotoxic stress responses...
January 21, 2017: Journal of Allergy and Clinical Immunology
Michael Förster, Rupinder K Boora, Jessica C Petrov, Nassima Fodil, Isabella Albanese, Jamie Kim, Philippe Gros, Anastasia Nijnik
Several previous studies outlined the importance of the histone H2A deubiquitinase MYSM1 in the regulation of stem cell quiescence and haematopoiesis. In this study we investigated the role of MYSM1 in T-cell development. Using mouse models that allow conditional Mysm1 ablation at late stages of thymic development, we found that MYSM1 is intricately involved in the maintenance, activation and survival of CD8(+) T cells. Mysm1 ablation resulted in a twofold reduction in CD8(+) T-cell numbers, and also led to a hyperactivated CD8(+) T-cell state accompanied by impaired proliferation and increased pro-inflammatory cytokine production after ex vivo stimulation...
May 2017: Immunology
Michael Förster, Kyo Farrington, Jessica C Petrov, Jad I Belle, Barbara C Mindt, Mariko Witalis, Claudia U Duerr, Jörg H Fritz, Anastasia Nijnik
MYSM1 is a chromatin-binding histone deubiquitinase. MYSM1 mutations in humans result in lymphopenia whereas loss of Mysm1 in mice causes severe hematopoietic abnormalities, including an early arrest in B cell development. However, it remains unknown whether MYSM1 is required at later checkpoints in B cell development or for B cell-mediated immune responses. We analyzed conditional mouse models Mysm1(fl/fl)Tg.mb1-cre, Mysm1(fl/fl)Tg.CD19-cre, and Mysm1(fl/fl)Tg.CD21-cre with inactivation of Mysm1 at prepro-B, pre-B, and follicular B cell stages of development...
November 28, 2016: Journal of Leukocyte Biology
Jing Li, Jiachen Wei, Pengcheng Xu, Mengdan Yan, Jingjie Li, Zhengshuai Chen, Tianbo Jin
We investigated the correlation between type 2 diabetes (T2D)-related genes and the clinical characteristics of T2D in the Chinese Han population. Our study included 319 patients and 387 controls. Age, gender, clinical features, medications intake and biochemical blood profiles were analyzed. Genotyping was performed on a total of 18 single nucleotide polymorphisms previously reported to be associated with T2D. Our analyses revealed that the CT genotype of ARHGAP22 rs4838605 is associated with T2D risk. Upon analyzing the subjects' clinical characteristics, we found that for rs2811893, the TT genotype correlated with high creatinine levels, while the AA genotype of rs17045754 and the TT genotype of rs4838605 correlated with elevated triglyceride levels...
December 20, 2016: Oncotarget
Jessica C Petrov, Anastasia Nijnik
Myb-Like SWIRM and MPN domains 1 (MYSM1) is a chromatin-binding protein, essential for hematopoietic stem cell (HSC) maintenance and differentiation in humans and mouse models. HSCs in mammalian bone marrow exist in close interactions with many non-hematopoietic cell types in their microenvironment, collectively known as the bone marrow niche. Although cell-intrinsic activities of MYSM1 within the hematopoietic cells are known to play an important role in hematopoietic homeostasis, Mysm1 expression is also widely observed in non-hematopoietic cells, and MYSM1 is implicated as an important regulator of mesenchymal stem cell differentiation, osteoblast function, and adipogenesis within the bone marrow...
March 2017: Experimental Hematology
Xiao-Xia Jiang, Yu Liu, Hong Li, Yaping Gao, Rong Mu, Jianping Guo, Jing Zhang, Yan-Mei Yang, Fengjun Xiao, Bing Liu, Changyong Wang, Beifen Shen, Si-Yi Chen, Zhanguo Li, Guang Yang
The aberrant expansion of B1a cells has been observed in several murine autoimmune disease models; however, the mechanism of such proliferation of B1a cells is still limited. Here, we identify that Myb Like, SWIRM And MPN Domains 1 (MYSM1), a histone H2A deubiquitinase, plays an intrinsic role in the proliferation of B1a cells where MYSM1 deficiency results in the increased proliferation of B1a cells in mice. We demonstrate that MYSM1 recruits c-Myc to the promoter of miR-150 and stimulates the transcription of miR-150...
October 18, 2016: Oncotarget
X F Huang, V Nandakumar, G Tumurkhuu, T Wang, X Jiang, B Hong, L Jones, H Won, H Yoshii, K Ozato, A Masumi, S-Y Chen
Mysm1(-/-) mice have severely decreased cellularity in hematopoietic organs. We previously revealed that Mysm1 knockout impairs self-renewal and lineage reconstitution of HSCs by abolishing the recruitment of key transcriptional factors to the Gfi-1 locus, an intrinsic regulator of HSC function. The present study further defines a large LSKs in >8-week-old Mysm1(-/-) mice that exhibit increased proliferation and reduced cell lineage differentiation compared with those of WT LSKs. We found that IRF2 and IRF8, which are important for HSC homeostasis and commitment as transcription repressors, were expressed at lower levels in Mysm1(-/-) HSCs, and Mysm1 enhanced function of the IRF2 and IRF8 promoters, suggesting that Mysm1 governs the IRFs for HSC homeostasis...
June 9, 2016: Cell Death & Disease
Ping Li, Yan-Mei Yang, Suzi Sanchez, Dian-Chao Cui, Rui-Jie Dang, Xiao-Yan Wang, Qiu-Xia Lin, Yan Wang, Changyong Wang, Da-Fu Chen, Si-Yi Chen, Xiao-Xia Jiang, Ning Wen
Deubiquitinase MYSM1 has been shown to play a critical role in hematopoietic cell differentiation and hematopoietic stem cell (HSC) maintenance. Mesenchymal stem cells (MSCs) are multipotent stromal cells within the bone marrow. MSCs are progenitors to osteoblasts, chondrocytes, adipocytes, and myocytes. Although, MSCs have been extensively studied, the roles of MYSM1 in these cells remain unclear. Here we describe the function of MYSM1 on MSC maintenance and differentiation. In this report, we found that Mysm1-/- mice had a lower bone mass both in long bone and calvaria compared with their control counterpart...
February 26, 2016: Scientific Reports
Swarupa Panda, Jonas A Nilsson, Nelson O Gekara
Pattern-recognition receptors (PRRs) including Toll-like receptors, RIG-I-like receptors, and cytoplasmic DNA receptors are essential for protection against pathogens but require tight control to avert inflammatory diseases. The mechanisms underlying this strict regulation are unclear. MYSM1 was previously described as a key component of epigenetic signaling machinery. We found that in response to microbial stimuli, MYSM1 accumulated in the cytoplasm where it interacted with and inactivated TRAF3 and TRAF6 complexes to terminate PRR pathways for pro-inflammatory and type I interferon responses...
October 20, 2015: Immunity
Xiao-Xia Jiang, YuChia Chou, Lindsey Jones, Tao Wang, Suzi Sanchez, Xue F Huang, Lei Zhang, Changyong Wang, Si-Yi Chen
B cell-mediated antibody response plays critical roles in protective immunity, as well as in the pathogenesis of allergic and autoimmune diseases. Epigenetic histone and DNA modifications regulate gene transcription and immunity; however, so far, little is known about the role of epigenetic regulation in antibody responses. In this study, we found that mice deficient in the histone H2A deubiquitinase MYSM1, despite their severe defect in B cell development, exhibit an enhanced antibody response against both T cell-dependent and independent antigens...
September 8, 2015: Scientific Reports
Tangui Le Guen, Fabien Touzot, Isabelle André-Schmutz, Chantal Lagresle-Peyrou, Benoit France, Laetitia Kermasson, Nathalie Lambert, Capucine Picard, Patrick Nitschke, Wassila Carpentier, Christine Bole-Feysot, Annick Lim, Marina Cavazzana, Isabelle Callebaut, Jean Soulier, Nada Jabado, Alain Fischer, Jean-Pierre de Villartay, Patrick Revy
BACKGROUND: Myb-Like, SWIRM, and MPN domains 1 (MYSM1) is a metalloprotease that deubiquitinates the K119-monoubiquitinated form of histone 2A (H2A), a chromatin marker associated with gene transcription silencing. Likewise, it has been reported that murine Mysm1 participates in transcription derepression of genes, among which are transcription factors involved in hematopoietic stem cell homeostasis, hematopoiesis, and lymphocyte differentiation. However, whether MYSM1 has a similar function in human subjects remains unclear...
December 2015: Journal of Allergy and Clinical Immunology
Michael Förster, Jad I Belle, Jessica C Petrov, Edward J Ryder, Simon Clare, Anastasia Nijnik
MYSM1 is a chromatin-interacting deubiquitinase recently shown to be essential for hematopoietic stem cell (HSC) function and normal progression of hematopoiesis in both mice and humans. However, it remains unknown whether the loss of function in Mysm1-deficient HSCs is due to the essential role of MYSM1 in establishing the HSC pool during development or due to a continuous requirement for MYSM1 in adult HSCs. In this study we, for the first time, address these questions first, by performing a detailed analysis of hematopoiesis in the fetal livers of Mysm1-knockout mice, and second, by assessing the effects of an inducible Mysm1 ablation on adult HSC functions...
August 15, 2015: Stem Cells and Development
Jad I Belle, David Langlais, Jessica C Petrov, Mercedes Pardo, Russell G Jones, Philippe Gros, Anastasia Nijnik
MYSM1 is a chromatin-binding transcriptional cofactor that deubiquitinates histone H2A. Studies of Mysm1-deficient mice have shown that it is essential for hematopoietic stem cell (HSC) function and lymphopoiesis. Human carriers of a rare MYSM1-inactivating mutation display similar lymphopoietic deficiencies. However, the mechanism by which MYSM1 regulates hematopoietic homeostasis remains unclear. Here, we show that Mysm1-deficiency results in p53 protein elevation in many hematopoietic cell types. p53 is a central regulator of cellular stress responses and HSC homeostasis...
April 9, 2015: Blood
M Gatzka, A Tasdogan, A Hainzl, G Allies, P Maity, C Wilms, M Wlaschek, K Scharffetter-Kochanek
Monoubiquitination of core histone 2A (H2A-K119u) has a critical role in gene regulation in hematopoietic differentiation and other developmental processes. To explore the interplay of histone H2A deubiquitinase Myb-like SWIRM and MPN domain containing1 (2A-DUB/Mysm1) with the p53 axis in the sequential differentiation of mature lymphocytes from progenitors, we systematically analyzed hematopoiesis and early T-cell development using Mysm1(-/-) and p53(-/-)Mysm1(-/-) mice. Mysm1(-/-) thymi were severely hypoplastic with <10% of wild-type cell numbers as a result of a reduction of early thymocyte progenitors in context with defective hematopoietic stem cells, a partial block at the double-negative (DN)1-DN2 transition and increased apoptosis of double-positive thymocytes...
September 2015: Cell Death and Differentiation
Tia DiTommaso, Lynelle K Jones, Denny L Cottle, Anna-Karin Gerdin, Valerie E Vancollie, Fiona M Watt, Ramiro Ramirez-Solis, Allan Bradley, Karen P Steel, John P Sundberg, Jacqueline K White, Ian M Smyth
The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP). A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression...
October 2014: PLoS Genetics
Haejung Won, Vijayalakshmi Nandakumar, Peter Yates, Suzi Sanchez, Lindsey Jones, Xue F Huang, Si-Yi Chen
The mechanisms controlling the development of dendritic cells (DCs) remain incompletely understood. Using an Mysm1 knockout (Mysm1(-/-)) mouse model, we identified the histone H2A deubiquitinase Mysm1, as a critical regulator in DC differentiation. Mysm1(-/-) mice showed a global reduction of DCs in lymphoid organs, whereas development of granulocytes and macrophages were not severely affected. Hematopoietic progenitors and DC precursors were significantly decreased in Mysm1(-/-) mice and defective in Fms-like tyrosine kinase-3(Flt3) ligand-induced, but not in granulocyte macrophage-colony-stimulating factor (GM-CSF)-induced DC differentiation in vitro...
October 23, 2014: Blood
Kifayathullah Liakath-Ali, Valerie E Vancollie, Emma Heath, Damian P Smedley, Jeanne Estabel, David Sunter, Tia Ditommaso, Jacqueline K White, Ramiro Ramirez-Solis, Ian Smyth, Karen P Steel, Fiona M Watt
Permanent stop-and-shop large-scale mouse mutant resources provide an excellent platform to decipher tissue phenogenomics. Here we analyse skin from 538 knockout mouse mutants generated by the Sanger Institute Mouse Genetics Project. We optimize immunolabelling of tail epidermal wholemounts to allow systematic annotation of hair follicle, sebaceous gland and interfollicular epidermal abnormalities using ontology terms from the Mammalian Phenotype Ontology. Of the 50 mutants with an epidermal phenotype, 9 map to human genetic conditions with skin abnormalities...
April 11, 2014: Nature Communications
Abdulrahman Alsultan, Hanan E Shamseldin, Mohamed Elfaki Osman, Mansour Aljabri, Fowzan S Alkuraya
No abstract text is available yet for this article.
November 28, 2013: Blood
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