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Interruption of Klf5 acetylation in basal progenitor cells promotes luminal commitment by activating Notch signaling

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Journal of genetics and Genomics 2022年第6期49卷 579-582页

作者： Baotong Zhang Siyuan Xia Mingcheng Liu Xiawei Li Shimin Shuai Wei Tao Yixiang Li Jianping Jenny Ni Wei Zhou Lan Liao Jianming Xu Jin-Tang Dong department of human Cell Biology and genetics Southern University of Science and Technology School of MedicineShenzhenGuangdong 518055China department of Hematology and Medical Oncology Emory University School of MedicineAtlantaGA 30322USA Winship Cancer institute Emory UniversityAtlantaGA 30322USA department of human Cell Biology and genetics Southern University of Science and 7.Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonTXUSA

Prostate homeostasis and regeneration rely on the proper function of adult stem/progenitor cells(Ousset et al., 2012), which have also been considered as potential cells of origin for prostate cancer(Visvader, 2011) given their key positions in the lineage hierarchy and self-renewal capability. Accumulating evidence reveals the existence of multipotent progenitor cells in both basal and luminal cells.

关键词： progenitor luminal

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Ultra-conserved non-coding sequences within the FOXF1 enhancer are critical for human lung development

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Genes & Diseases 2022年第6期9卷 1423-1426页

作者： Przemyslaw Szafranski Tadeusz Majewski Esra Yıldız Bolukbası Tomasz Gambin Justyna A.Karolak Nahir Cortes-Santiago Markus Bruckner Gabriele Amann Denisa Weis Paweł Stankiewicz department of Molecular&human genetics Baylor College of MedicineHoustonTX 77030USA institute of Computer Science Warsaw University of TechnologyWarsaw 00-665Poland Chair and department of genetics and Pharmaceutical Microbiology Poznan University of Medical SciencesPoznan 60-806Poland department of pathology Texas Children’s HospitalHoustonTX 77030USA department of pathology&Immunology Baylor College of MedicineHoustonTX 77030USA department of Anaesthesia Kepler University Medical Campus IIILinz 4020Austria department of pathology Medical University of ViennaVienna 1090Austria department of Medical genetics Kepler University Hospital Med Campus IVJohannes Kepler University LinzLinz 4020Austria

Heterozygous single nucleotide variants(SNVs)or copynumber variant(CNV)deletions,involving the mesenchymal forkhead box family transcription factor gene,FOXF1,or its distant lung-specific enhancer,are responsible for 80%e90%of cases of alveolar capillary dysplasia with misalignment of pulmonary veins(ACDMPV).1 ACDMPV is a lethal lung developmental disorder with severe progressive respiratory failure and persistent pulmonary arterial hypertension(Supplemental Material).Intriguingly,in contrast to point mutations in FOXF1,the ACDMPV-causative CNV deletions arise de novo almost exclusively on the maternal chromosome 16q24.1.

关键词： lung respiratory capillary

AICAR inhibits proliferation and induced S-phase arrest,and promotes apoptosis in CaSki cells

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Acta Pharmacologica Sinica 2007年第12期28卷 1984-1990页

作者： Tong-ju GUAN~2,Feng-jin QIN~3,Jian-hai DU~4,Li Geng~3,You-yi ZHANG~(4,5),Min LI~(2,5)~2 institute of pathology,The School of Basic medicine,Lanzhou University,Lanzhou 730000,China ~3 department of Gynaecology andObstetrics,Peking University Third Hospital,Beijing 100083,China ~4 institute of Vascular medicine,Peking University Third Hospital andKey laboratory of Molecular Cardiovascular Sciences Ministry of Education,Beijing 100083,China institute of pathology The School of Basic Medicine Lanzhou University Lanzhou China department of Gynaecology and Obstetrics Peking University Third Hospital Beijing China institute of Vascular medicine Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing China

Aim:The aim of the present study was to determine the effect of 5-aminoimidazole-4-carboxamide-ribonucleoside （AICAR） on proliferation,cell cycle,and apoptosisin the human epithelial cervical cancer cell line CaSki ***:Cell countand 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay were usedto determine cell proliferation and *** 33258 staining was con-ducted to distinguish the apoptotic *** cycle and Annexin-V/propidiumiodide staining were analyzed by fluorescence-activated cell sorting （FACS）.AWestern blot assay was used to evaluate the expression of AKT （also known asprotein kinase B）,mammalian target of rapamycin （mTOR）,p53,and extracellularsignal-regulated kinase （ERK）.Results:AICAR （500 μmol/L） significantly inhibi-ted the proliferation of CaSki cells treated for 24,48,and 72 h as determined by *** cells at the G1and G2phases were dramatically decreased while cells atthe S phase were increased in response to AICAR treatment for 24,48,and 72 *** MTT assay showed less viable cells and Hoechst fluorescent staining showedmore apoptotic cells upon AICAR *** results of the Annexin-Vstaining demonstrated a time-dependent increase of apoptosis in cells treatedwith AICAR for 24,36,and 48 ***,AICAR activated caspase-3 in atime-dependent *** was also found that AICAR inhibited the phosphory-lation of AKT and mTOR,which are important kinases regulating cell growth *** stimulation obviously increased the expression of the tumorsuppressor p53 and the phosphorylation of ***:AICAR inhibitedproliferation and induced S phase arrest and promoted apoptosis in CaSki cells,which might be mediated by the downregulation of the AKT/mTOR pathway andthe upregulation of the p53/ERK pathway.

关键词： AICAR proliferation apoptosis CaSki cells

Atm deficient zebrafish model reveals conservation of the tumour suppressor function and a role in fertility

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Genes & Diseases 2023年第2期10卷 381-384页

作者： Jeroen Vierstraete Charlotte Fieuws David Creytens Jo Van Dorpe Andy Willaert Anne Vral Kathleen BM Claes Center for Medical genetics Department of Biomolecular MedicineGhent University Hospital and Ghent University9000 GhentBelgium department of human Structure and Repair Ghent University9000 GhentBelgium Cancer Research institute Ghent (CRIG) Ghent University and Ghent University Hospital9000 GhentBelgium department of pathology Ghent University and Ghent University Hospital9000 GhentBelgium

Biallelic loss-of-function variants in ATM (Ataxia Telangiectasia Mutated) cause Ataxia Telangiectasia (AT), a rare disorder associated with cerebellar degeneration and ataxia, cancer predisposition, infertility, growth retardation, etc. ATM is a phosphoinositide 3-kinase-related kinase (PIKK) with a role in DNA repair and maintenance of genome stability. Studying a multisystem genetic disease like AT requires animal models to ascertain its pathogenesis at the level of tissues, organs and the organism. Due to its small size, cheap maintenance, large progeny, rapid development and initial transparency, zebrafish (Danio rerio) is an increasingly popular vertebrate model organism, suitable for genetic modifications and large-scale in vivo therapeutic screens as embryos are chemically permeable to small compounds. Currently, no zebrafish model for AT exists.1 We generated atm knock-outs through CRIPSR-Cas9 mutagenesis. We show that atm conserved its function as a tumour suppressor gene and is involved in gametogenesis and fertility. Therefore, this mutant is of great value for further studies investigating the role of atm in reproduction and tumorigenesis.

关键词： ATM function transparency

A combination of follicle stimulating hormone, estradiol and age is associated with the pregnancy outcome for women undergoing assisted reproduction: a retrospective cohort analysis

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Science China(Life Sciences) 2019年第1期62卷 112-118页

作者： Ziru Jiang Li Jin Weihui Shi Ji Xi Yulian Hu Xinmei Liu Jianzhong Sheng Guolian Ding Hefeng Huang The International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University institute of Embryo-Fetal Original Adult Disease Shanghai Key Laboratory for Reproductive Medicine School of Medicine Shanghai Jiao Tong University department of pathology and Pathophysiology School of Medicine Zhejiang University

To investigate the effect of basal hormone levels including follicle stimulating hormone(FSH) and estradiol(E2) and age on the pregnancy outcomes in women undergoing in vitro fertilization and embryo transfer(IVF-ET), we designed a retrospective cohort analysis and collected information of patients undergoing IVF between January 2014 and April 2017. We found that young women had much better pregnancy outcomes than older women regardless of the hormone levels. The pregnancy outcomes declined in young women with high basal E2, even though they had normal FSH. Older women with higher FSH had a worse outcome of pregnancy, especially with increased E2 level. The results suggest that a combination of FSH, E2 and age could effectively predict the pregnancy outcome for women undergoing IVF-ET, and we should encourage infertile women with diminished ovarian reserve, especially young infertile women, to try the assisted reproduction as early as possible. After 40-yearold, the cost-benefit ratio should be considered according to the ovarian function.

关键词： follicle stimulating hormone estradiol age pregnancy outcome assisted reproduction

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Nucleoporin 35 regulates cardiomyocyte pH homeostasis by controlling Na^(+)-H^(+)exchanger-1 expression

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分子细胞生物学报:英文版 2015年第5期7卷 476-485页

作者： Liang Xu Lei Pan Jun Li Bijun Huang Jing Feng Changming Li ShiyiWang Erlinda The Yuan Liu Tianyou Yuan Lixiao Zhen Dandan Liang Yi Liu Li Li Yingyu Cui Xiaoyan Jiang Luying Peng Yi-Han Chen Key laboratory of Arrhythmias of the Ministry of Education of China Shanghai East HospitalTongji University School of MedicineShanghai 200120China Research Center for Translational medicine Shanghai East HospitalTongji University School of MedicineShanghai 200120China institute of Medical genetics Tongji UniversityShanghai 200092China department of Cardiology Shanghai East HospitalTongji University School of MedicineShanghai 200120China department of pathology and Pathophysiology Tongji University School of MedicineShanghai 200092China

The mammalian nuclear pore complex is comprised of∼30 different nucleoporins(Nups).It governs the nuclear import of gene expression modulators and the export of *** cardiomyocytes,Na1-H1 exchanger-1(NHE1)is an integral membrane protein that exclusively regulates intracellular pH(pHi)by exchanging one intracellular H1 for one extracellular ***,the role of Nups in cardiac NHE1 expression remains *** herein report that Nup35 regulates cardiomyocyte NHE1 expression by controlling the nucleo-cytoplasmic trafficking of nhe1 *** N-terminal domain of Nup35 determines nhe1 mRNA nuclear export by targeting the 5′-UTR(2412 to2213 nt)of ***35 ablationweakensthe resistance of cardiomyocytes to an acid challenge by depressingNHE1 ***,we identify thatNup35 andNHE1 are simultaneously downregulated in ischemic cardiomyocytes both in vivo and in *** expression of Nup35 effectively counteracts the anoxia-induced intracellular *** conclude that Nup35 selectively regulates cardiomyocyte pHi homeostasis by posttranscriptionally controlling NHE1 *** finding reveals a novel regulatory mechanism of cardiomyocyte pHi,and may provide insight into the therapeutic strategy for ischemic cardiac diseases.

关键词： cardiomyocyte intracellular pH Na^(+)-H^(+)exchanger nuclear pore complex nucleo-cytoplasmic transport

Mechanism and pathobiologic implications of CHFR promoter methylation in gastric carcinoma

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World Journal of Gastroenterology 2008年第32期14卷 5000-5007页

作者： Yu-Jia Gao Yan Xin lian-Jun Zhang Jin Zhou The Fourth laboratory of Cancer institute & department of Tumor pathology of General Surgery institute The First Affiliated Hospital of China Medical University Shengyang 110001 Liaoning Province China department of Surgery and Internal medicine Liaoning Tumor Hospital Shengyang 110042 Liaoning Province China

AIM： TO investigate the aberrant methylation of CHFR promoter in human gastric cancer （GC） and its impact on the expression of CHFR mRNA and protein, as well as its correlation with clinical and histological features of human GC. METHODS： Methylation-specific polymerase chain reaction （MSPCR） was used to detect the methylation status of CHFR promoter in 20 primary GC samples and paired normal gastric mucosa. The CHFR mRNA and protein expressions were investigated both by RT-PCR and by Western blotting. The CHFR protein expression in 39 GC samples was immunohistochemically examined. RESULTS： The DNA methylation of the CHFR gene was found in 9 of the 20 GC samples （45%） and the down-regulation of CHFR mRNA and protein was significantly associated with the methylation status of the CHFR gene （P = 0.006）. In 20 samples of corresponding non-neoplastic mucosa, no DNA methylation of the CHFR gene was detected. The CHFR gene methylation in poorly differentiated GC samples was significantly higher than that in well-differentiated GC samples （P = 0.014）. Moreover, the negative CHFR protein expression rate in paraffin-embedded GC samples was 55.07% （38/69）, the positive rate in poorly differentiated GC samples was 36.73% （18/49）, which was significantly lower than 65.00% （13/20） in well-differentiated GC samples （X^2 = 4.586, P = 0.032）. CONCLUSION： Aberrant methylation of the CHFR gene may be involved in the carcinogenesis and development of GC, and is the predominant cause of down-regulation or loss of CHFR mRNA or protein expression. As aberrant methylation of CHFR promoter is correlated with tumor differentiation, it may help to predict the prognosis of GC and CHFR may become a novel target of gene therapy for GC in the future.

关键词： CHFR gene Gastric carcinoma DNA methylation

Expression of human hepatic lipase negatively impacts apolipoprotein A-Ⅰ production in primary hepatocytes from Lipc-null mice

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The Journal of Biomedical Research 2014年第3期28卷 201-212页

作者： Michelle Bamji-Mirza Wandong Zhang Zemin Yao department of Biochemistry Microbiology & ImmunologyUniversity of Ottawa department of pathology and laboratory medicine University of Ottawa human Health Therapeutics Portfolio Life Sciences DivisionNational Research Council Canada Ottawa institute of Systems Biology University of Ottawa

This study aimed to examine whether expression of human hepatic lipase（hHL） exerted an intracellular effect on hepatic production of apolipoprotein（apo） *** levels of secreted and cell-associated apoA-I were contrasted between primary hepatocytes isolated from Lipc-nuW and C57BL/6 mice,and between Lipc-nuW hepatocytes transfected with either hHL-encoding or control *** HSPG-binding deficient hHL protein（hHLmt） was used to determine the impact of cell surface binding on HL *** of apoA-I in conditioned media of primary hepatocytes isolated from Lipc-nuW mice was increased as compared to that from C57BL/6 *** labeling experiments showed that secretion of ＇＇S-apoA-I from Lipc-nuW cells was significantly higher than that from C57BL/6 *** of hHL in Lipc-nuW hepatocytes,through adenovirus-mediated gene transfer,resulted in decreased synthesis and secretion of ＇S-apoA-I,but not S-apoE,as compared with cells transfected with control *** of HSPG-binding deficient hHLmt in Lipc-nuW cells also exerted an inhibitory effect on apoA-I production,even though hHLmt displayed impaired exit from the endoplasmic reticulum as compared with *** fractionation revealed that expression of hHL or hHLmt led to increased microsome-association of apoA-I relative to non-transfected *** of hHL negatively impacts hepatic production of apoA-I.

关键词： high density lipoprotein heparan sulphate proteoglycans ABCA1 endoplasmic reticulum adenovirus

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Plasticity of male germline stem cells and their applications in reproductive and regenerative medicine

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Asian Journal of Andrology 2015年第3期17卷 367-372页

作者： Zheng Chen Zheng Li Zuping He State Key laboratory of Oncogenes and Related Genes Renji-Med X Clinical Stem Cell Research Center Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai Institute of Cancer Shanghai 200127 China department of Urology Shanghai Human Sperm Bank Shanghai Institute of Andrology Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200001 China Shanghai Key laboratory of Assisted Reproduction and Reproductive genetics Shanghai 200127 China Shanghai Key laboratory of Reproductive medicine Shanghai 200025 China

Spermatogonial stem cells （SSCs）, also known as male germline stem cells, are a small subpopulation of type A spermatogonia with the potential of self-renewal to maintain stem cell pool and differentiation into spermatids in mammalian testis. SSCs are previously regarded as the unipotent stem cells since they can only give rise to sperm within the seminiferous tubules. However, this concept has recently been challenged because numerous studies have demonstrated that SSCs cultured with growth factors can acquire pluripotency to become embryonic stem-like cells. The in vivo and in vitro studies from peers and us have clearly revealed that SSCs can directly transdifferentiate into morphologic, phenotypic, and functional cells of other lineages. Direct conversion to the cells of other tissues has important significance for regenerative medicine. SSCs from azoospermia patients could be induced to differentiate into spermatids with fertilization and developmental potentials. As such, SSCs could have significant applications in both reproductive and regenerative medicine due to their unique and great potentials. In this review, we address the important plasticity of SSCs, with focuses on their self-renewal, differentiation, dedifferentiation, transdifferentiation, and translational medicine studies.

关键词： differentiation direct transdifferentiation pluripotency self-renewal spermatogonial stem cells