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Oncogenic MORC2 in cancer development and beyond

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Genes & Diseases 2024年第2期11卷 861-873页

作者： Shan Zhang Ayao Guo Huan Wang Jia Liu Chenshuang Dong Junyi Ren Guiling Wang Key laboratory of cell biology Department of Cell BiologyMinistry of Public Health and Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyangLiaoning 110122China Department of Breast Surgery The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110001China

Microrchidia CW-type zinc finger 2(MORC2)is a member of the MORC superfamily of nuclear *** evidence has shown that MORC2 not only participates in gene transcription and chromatin remodeling but also plays a key in human disease and tumor development by regulating the expression of downstream oncogenes or tumor *** present review provides an updated overview of MORC2 in the aspect of cancer hallmark and therapeutic resistance and summarizes its upstream regulators and downstream target *** systematic review may provide a favorable theoretical basis for emerging players of MORC2 in tumor development and new insight into the potential clinical application of basic science discoveries in the future.

关键词： Cancer development Hallmarks of cancer MORC2 Therapeutic target Treatment resistance

Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms

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Journal of Molecular cell biology 2024年第1期16卷 15-28页

作者： Te Li Min Liu Fan Yu Song Yang Weiwen Bu Kai Liu Jia Yang Hua Ni Mulin Yang Hanxiao Yin Renjie Hong Dengwen Li Huĳie Zhao Jun Zhou Haihe laboratory of cell Ecosystem State Key Laboratory of Medicinal Chemical BiologyTianjin Key Laboratory of Protein ScienceCollege of Life SciencesNankai UniversityTianjin 300071China laboratory of Tissue Homeostasis Haihe Laboratory of Cell EcosystemTianjin 300462China Center for cell Structure and Function Collaborative Innovation Center of Cell Biology in Universities of ShandongShandong Provincial Key Laboratory of Animal Resistance BiologyCollege of Life SciencesShandong Normal UniversityJinan 250014China

Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan ***,the mechanistic link of cilia to CMD complications is still poorly ***,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar ***,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl *** studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium *** vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm *** findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.

关键词： carbohydrate metabolism disorder aldose aldehyde cilium disassembly formyl group calcium influx HDAC6

Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice

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Journal of Genetics and Genomics 2024年第4期51卷 407-418页

作者： Yaling Wang Xueying Huang Guoying Sun Jingwen Chen Bangguo Wu Jiahui Luo Shuyan Tang Peng Dai Feng Zhang Jinsong Li Lingbo Wang Shanghai Key laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shanghai Key laboratory of Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key laboratory of cell biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

During spermiogenesis,haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes,which are required for successful *** deformities in flagella cause a male infertility syndrome,multiple morphological abnormalities of the flagella(MMAF),while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental ***,evidence regarding the occurrence of acrosomal hypoplasia in MMAF is ***,we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38(Ccdc38)via inducing a nonsense mutation and find that the males are *** Ccdc38-KO sperm display acrosomal hypoplasia and typical MMAF *** find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO *** analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3,a protein associated with acrosome biogenesis,in testes and an aberrant distribution of TEKT3 in *** finally show that intracytoplasmic sperm injection overcomes Ccdc38-related *** study thus reveals a previously unknown role for CCDC38 in acrosome biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF.

关键词： Acrosomal hypoplasia Multiple morphological abnormalities of the flagella(MMAF) Infertility Sperm motility Asthenoteratozoospermia Disease modeling

Heat Shock Factor A1s are required for phytochrome-interacting factor 4-mediated thermomorphogenesis in Arabidopsis

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Journal of integrative Plant biology 2024年第1期66卷 20-35页

作者： Bingjie Li Shimeng Jiang Liang Gao Wenhui Wang Haozheng Luo Yining Dong Zhihua Gao Shuzhi Zheng Xinye Liu Wenqiang Tang Key laboratory of Molecular and cellular biology of Ministry of Education Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell SignalingHebei Key Laboratory of Molecular and Cellular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China School of Information Technology Hebei University of Economics and BusinessShijiazhuang 050061China

Thermomorphogenesis and the heat shock(HS)response are distinct thermal responses in plants that are regulated by PHYTOCHROME-INTERACTING FACTOR 4(PIF4)and HEAT SHOCK FACTOR A1s(HSFA1s),*** is known about whether these responses are interconnected and whether they are activated by similar *** analysis of transcriptome dynamics in response to warm temperature(28℃)treatment revealed that 30 min of exposure activated the expression of a subset of HSFA1 target genes in Arabidopsis ***,a loss-of-function HSFA1 quadruple mutant(hsfa1-cq)was insensitive to warm temperature-induced hypocotyl *** hsfa1-cq plants grown at 28℃,the protein and transcript levels of PIF4 were greatly reduced,and the circadian rhythm of many thermomorphogenesis-related genes(including PIF4)was ***,the nuclear localization of HSFA1s and the binding of HSFA1d to the PIF4 promoter increased following warm temperature exposure,whereas PIF4 overexpression in hsfa1-cq partially rescued the altered warm temperature-induced hypocotyl growth of the *** together,these results suggest that HSFA1s are required for PIF4 accumulation at a warm temperature,and they establish a central role for HSFA1s in regulating both thermomorphogenesis and HS responses in Arabidopsis.

关键词： HSFA1 PIF4 thermomorphogenesis

The evolving views of hematopoiesis:from embryo to adulthood and from in vivo to in vitro

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Journal of Genetics and Genomics 2024年第1期51卷 3-15页

作者： Yifan Zhang Feng Liu Shandong Provincial Key laboratory of Animal cell and Developmental biology School of Life SciencesShandong UniversityQingdaoShandong 266237China State Key laboratory of Membrane biology Institute of ZoologyInstitute for Stem Cell and RegenerationUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China

The hematopoietic system composed of hematopoietic stem and progenitor cells(HSPCs)and their differentiated lineages serves as an ideal model to uncover generic principles of cell fate *** gastrulation onwards,there successively emerge primitive hematopoiesis(that produces specialized he-matopoietic cells),pro-definitive hematopoiesis(that produces lineage-restricted progenitor cells),and definitive hematopoiesis(that produces multipotent HSPCs).These nascent lineages develop in several transient hematopoietic sites and finally colonize into lifelong hematopoietic *** development and maintenance of hematopoietic lineages are orchestrated by cell-intrinsic gene regulatory networks and cell-extrinsic microenvironmental *** to the progressive methodology(e.g.,high-throughput lineage tracing and single-cell functional and omics analyses),our understanding of the developmental origin of hematopoietic lineages and functional properties of certain hematopoietic organs has been updated;meanwhile,new paradigms to characterize rare cell types,cell heterogeneity and its causes,and comprehensive regulatory landscapes have been ***,we review the evolving views of HSPC biology during developmental and postnatal ***,we discuss recent advances in the in vitro induction and expansion of HSPCs,with a focus on the implications for clinical applications.

关键词： Hematopoietic stem and progenitor cell Developmental hematopoiesis Postnatal hematopoiesis In vitro hematopoiesis

Identification and characterization of human hematopoietic mesoderm

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Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou State Key laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China CAMS Center for Stem cell Medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China Division of cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage *** is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental *** this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic *** discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM ***,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its *** of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell *** conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation

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Science China(Life Sciences) 2024年第5期67卷 1035-1050页

作者： Yaling Wang Jingwen Chen Xueying Huang Bangguo Wu Peng Dai Feng Zhang Jinsong Li Lingbo Wang State Key laboratory of Genetic Engineering Shanghai Key Laboratory of Metabolic Remodeling and HealthInstitute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China NHC Key Lab of Reproduction Regulation(Shanghai Institute for Biomedical and Pharmaceutical Technologies) School of PharmacyFudan UniversityShanghai 200433China Shanghai Key laboratoryof Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchoolof Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key laboratory of cell biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

Cytosine base editing achieves C·G-to-T·A substitutions and can convert four codons(CAA/CAG/CGA/TGG)into STOP-codons(induction of STOP-codons,iSTOP)to knock out genes with reduced *** enables direct phenotyping in founders’somatic cells,but it remains unknown whether this works in founders’germ cells so as to rapidly reveal novel genes for ***,we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders’germ cells:Cfap43-iSTOP male founders manifest expected sperm features resembling human“multiple morphological abnormalities of the flagella”syndrome(i.e.,MMAF-like features),while oocytes of Zp3-iSTOP female founders have no zona *** further illustrate iSTOP’s utility for dissecting the functions of unknown genes with Ccdc183,observing MMAF-like features and male infertility in Ccdc183-iSTOP founders,phenotypes concordant with those of Ccdc183-KO *** ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar *** study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation,and rapidly reveals the essentiality of Ccdc183 in fertility,thus providing a time-saving approach for validating genetic defects(like nonsense mutations)for human infertility.

关键词： disease modeling infertility multiple morphological abnormalities of the flagella(MMAF) induction of STOP-codons(iSTOP CRISPR-STOP) sperm motility

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Simple and robust 3D MINFLUX excitation with a variable phase plate

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Light(Science & Applications) 2024年第7期13卷 1354-1363页

作者： Takahiro Deguchi Jonas Ries European Molecular biology laboratory Cell Biology and BiophysicsHeidelbergGermany. Max Perutz Labs Vienna Biocenter Campus(VBC)ViennaAustria. University of Vienna Center for Molecular BiologyDepartment of Structural and Computational BiologyViennaAustria. University of Vienna Faculty of PhysicsViennaAustria

MINFLUX has achieved extraordinary resolution in superresolution imaging and single fluorophore *** is based on localizing single fluorophores by rapid probing with a patterned beam that features a local intensity *** implementations,however,are complex and expensive and are limited in speed and ***,we show that a combination of an electro-optical modulator with a segmented birefringent element such as a spatial light modulator produces a variable phase plate for which the phase can be scanned on the MHz *** or top-hat phase patterns generate high-contrast compact excitation point-spread functions for MINFLUX localization in the x,y,and z-direction,respectively,which can be scanned across a fluorophore within a microsecond,switched within 60 microseconds and alternated among different excitation *** discuss how to compensate for non-optimal performance of the components and present a robust 3D and multi-color MINFLUX excitation module,which we envision as an integral component of a high-performance and cost-effective open-source MINFLUX.

关键词： excitation phase switched

Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis

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Asian Journal of Andrology 2024年第2期26卷 212-219页

作者： Gao-Qing Qian Xiao-Chen Wang Xi Zhang Bin Shen Qiang Liu State Key laboratory of Reproductive Medicine and Offspring Health Nanjing Medical UniversityNanjing 211166China Shanghai Key laboratory of Reproductive Medicine Department of HistoembryologyGenetics and Developmental BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China State Key laboratory of Molecular biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China

Male germ cells employ specific metabolic pathways throughout their developmental *** a previous study,we discovered heightened expression of pyruvate kinase M(PKM),a pivotal glycolytic enzyme,in spermatogonia and *** gain deeper insights into PKM's roles in spermatogenesis,sperm function,and male fertility,we engineered a conditional-knockout mouse model(Pkm-vkO mice)to selectively disrupt the Pkm gene within germ *** maintaining regular testicular histology and sperm morphology,the male Pkm-vko mice were infertility,characterized by significant impairments in sperm motility and adenosine triphosphate(ATP)*** addition,Pkm-null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation,as well as compromised performance in in vitro fertilization *** conclude,PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells;however,it emerges as a critical factor influencing sperm motility and overall male fertility.

关键词： glycolysis male fertility pyruvate kinase M sperm motility spermatogenesis