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Differential regulation of H3S10 phosphorylation, mitosis progression and cell fate by Aurora Kinase B and C in mouse preimplantation embryos

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Protein & cell 2017年第9期8卷 662-674页

作者： Wenzhi Li Peizhe Wang Bingjie Zhang Jing Zhang Jia Ming Wei Xie Jie Na Center for Stem cell Biology and Regenerative Medicine School of Medicine Tsinghua University Beijing 100084 China Center for Stem cell Biology and Regenerative Medicine MOE Key Laboratory of Bioinformatics THU-PKU Center for LifeSciences School of Life Sciences Tsinghua University Beijing 100084 China

Coordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B （AurkB） is ubiquitously expressed while Aurora kinase C （AurkC） is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect. The kinase domains of AurkB and AurkC were responsible for their different ability to phosphorylate Histone H3 Serine 10 （H3S10P） and regulate metaphase timing. Using an Oct4-photoactivat- able GFP fusion protein （Oct4-paGFP） and fluorescence decay after photoactivation assay, we found that AurkB overexpression reduced Oct4 retention in the nucleus. Finally, we show that blastomeres with higher AurkC level elevated pluripotency gene expression, which were inclined to enter the inner cell mass lineage and subsequently contributed to the embryo proper. Collectively, our results are the first demonstration that the activity of mitotic kinases can influence cell fate decisions in mammalian preimplantation embryos and have important implications to assisted reproduction.

关键词： Aurora kinase mouse preimplantation embryo cell fate development mitosis

A Helm model for microRNA regulation in cell fate decision and conversion

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Science China(Life Sciences) 2013年第10期56卷 897-906页

作者： XIE ShuJuan ZHANG Yin QU LiangHu XU Hui Key Laboratory of Gene Engineering of Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen University

microRNAs （miRNAs） constitute a unique class of endogenous small non-coding RNAs that regulate gene expression post-transcriptionally. Studies over the past decade have uncovered a r^curring paradigm in which miRNAs are key regulators of cellular behavior under various physiological and pathological conditions. Most surprising is the recent observation that miRNAs have emerged as competent players in somatic cell reprogramming, suggesting an especially significant role for these small RNAs in cell fate settings. Here, we discuss the possible mechanisms underlying miRNA-mediated cell programming （i.e., the development and differentiation of embryonic stem cells） and reprogramming （i.e., turning somatic cells into pluripo- tent stem cells or other lineages）, and provide a ＂Helm＂ model of miRNAs in cell fate decision and conversion.

关键词： miRNA(s) cell fate development differentiation embryonic stem cells reprogramming iPS transdifferentiation

Putting things in place for fertilization： discovering roles for importin proteins in cell fate and spermatogenesis

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Asian Journal of Andrology 2015年第4期17卷 537-544页

作者： Kate L Loveland Andrew T Major Romaly Butler Julia C Young David A Jan Yoichi Miyamoto Department of Biochemistry and Molecular Biology Monash University Clayton VIC Australia Department of Anatomy and Developmental Biology Monash UniversityClayton VlC Australia Hudson Institute of Medical Research Monash Medical Centre Clayton VlC Australia School of Clinical Sciences Monash University ClaytonVlC Laboratory of Nuclear Transport Dynamics National Institutes of Biomedical Innovation Health and Nutrition Osaka Japan.

Importin proteins were originally characterized for their central role in protein transport through the nuclear pores, the only intracellular entry to the nucleus. This vital function must be tightly regulated to control access by transcription factors and other nuclear proteins to genomic DNA, to achieve appropriate modulation of cellular behaviors affecting cell fate. Importin-mediated nucleocytoplasmic transport relies on their specific recognition of cargoes, with each importin binding to distinct and overlapping protein subsets. Knowledge of importin function has expanded substantially in regard to three key developmental systems： embryonic stem cells, muscle cells and the germ line. In the decade since the potential for regulated nucleocytoplasmic transport to contribute to spermatogenesis was proposed, we and others have shown that the importins that ferry transcription factors into the nucleus perform additional roles, which control cell fate. This review presents key findings from studies of mammalian spermatogenesis that reveal potential new pathways by which male fertility and infertility arise. These studies of germline genesis illuminate new ways in which importin proteins govern cellular differentiation, includ ng v a d rect ng proteins to d st nct ntrace ular compartments and by determining cellular stress responses.

关键词： cell fate cell stress importin karyopherin nucleocytoplasmic transport spermatid spermatocyte spermatogenesis

pRb-E2F signaling in life of mesenchymal stem cells:cell cycle,cell fate,and cell differentiation

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Genes & Diseases 2014年第2期1卷 174-187页

作者： Boris Popov Nikolay Petrov Institute of Cytology Russian Academy of SciencesSt.Petersburg4Tikhoretsky Av.194064Russia

Mesenchymal stem cells(MSCs)are multipotent cells that can differentiate into various mesodermal lines forming fat,muscle,bone,and other lineages of connective *** possess plasticity and under special metabolic conditions may transform into cells of unusual phenotypes originating from ecto-and *** transplantation,MSCs release the humoral factors promoting regeneration of the damaged *** last five years,the numbers of registered clinical trials of MSCs have increased about 10 *** gives evidence that MSCs present a new promising resource for cell therapy of the most dangerous *** efficacy of the MSCs therapy is limited by low possibilities to regulate their conversion into cells of damaged tissues that is implemented by the pRb-E2F *** widely accepted viewpoint addresses pRb as ubiquitous regulator of cell cycle and tumor ***,current publications suggest that basic function of the pRb-E2F signaling in development is to regulate cell fate and *** facultative and constitutive chromatin modifications,pRb-E2F signaling promotes transient and stable cells quiescence,cell fate choice to differentiate,to senesce,or to *** of pRb is associated with cancer cell *** regulates cell fate by retaining quiescence of one cell population in favor of commitment of another or by suppression of genes of different cell *** is the founder member of the“pocket protein”family possessing functional *** increase in the efficacy of the MSCs based cell therapy will depend on precise understanding of various aspects of the pRb-E2F signaling.

关键词： cell cycle cell differentiation cell fate Mesenchymal stem cells pRb-E2F signaling

Novel insights into cell cycle regulation of cell fate determination

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2019年第6期20卷 467-475页

作者： Su-wei GAO Feng LIU State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of Sciences Institute for Stem cell and Regeneration Chinese Academy of Sciences University of Chinese Academy of Sciences

The stem/progenitor cell has long been regarded as a central cell type in development,homeostasis,and regeneration,largely owing to its robust self-renewal and multilineage differentiation *** balance between self-renewal and stem/progenitor cell differentiation requires the coordinated regulation of cell cycle progression and cell fate *** studies have demonstrated that cell cycle states determine cell fates,because cells in different cell cycle states are characterized by distinct molecular features and functional *** advances in high-resolution epigenome profiling,single-cell transcriptomics,and cell cycle reporter systems have provided novel insights into the cell cycle regulation of cell fate ***,we review recent advances in cell cycle-dependent cell fate determination and functional heterogeneity,and the application of cell cycle manipulation for cell fate *** findings will provide insight into our understanding of cell cycle regulation of cell fate determination in this field,and may facilitate its potential application in translational medicine.

关键词： cell cycle cell fate Heterogeneity fate conversion Stem/progenitor cell

A self-activation loop maintains stem cell fate for branching

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A self-activation loop maintains stem cell fate for branchin...

Macrophage-derived extracellular vesicles regulate skeletal stem/progenitor cell lineage fate and bone deterioration in obesity

2018全国植物生物学大会

作者： Xiuwei Cao Yuling Jiao State Key Laboratory of Plant Genomics Institute of Genetics and Developmental BiologyChinese Academy of Sciences

Plants differ from most animals in their retained ability to initiate new cycles of growth and development,which relies on the establishment and activity of branch *** seed plants,branching is achieved by axillary meristems,which are established in the axil of each leaf base and develop into lateral *** meristems are initiated from a meristematic cell population originally detached from the shoot apical *** remains unclear how the meristematic cell fate is *** we show that the meristem marker gene SHOOT MERISTEMLESS(STM) can activates its own expression to enable cell fate ***,the self-activation loop requires an STM-interacting protein FEWER AXILLARY BRANCHING(FAB),whose mutants display compromised axillary bud *** and biochemical data suggest that the STM-FAB heterodimer binds and activates STM as well as additional axillary meristem regulatory *** together,our finding provides a striking example in which a self-activation loop maintains the meristematic cell fate to enable branching.

关键词： meristem stem cell cell lineage cell fate branching

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Bioactive Materials 2024年第6期36卷 508-523页

作者： Chen He Chen Hu Wen-Zhen He Yu-Chen Sun Yangzi Jiang Ling Liu Jing Hou Kai-Xuan Chen Yu-Rui Jiao Mei Huang Min Huang Mi Yang Qiong Lu Jie Wei Chao Zeng Guang-Hua Lei Chang-Jun Li Department of Endocrinology Endocrinology Research CenterXiangya Hospital of Central South UniversityChangshaHunan410008China School of Biomedical Sciences Institute for Tissue Engineering and Regenerative MedicineFaculty of MedicineThe Chinese University of Hong KongHong Kong SARChina Center for Neuromusculoskeletal Restorative Medicine(CNRM) The Chinese University of Hong KongHong Kong SARChina Key Laboratory for Regenerative Medicine Ministry of EducationSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongHong Kong SARChina Department of Pharmacy The Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China Department of Orthopaedics Xiangya Hospital of Central South UniversityChangshaHunan410008China Department of Epidemiology and Health Statistics Xiangya School of Public HealthCentral South UniversityChangshaHunan410008China Hunan Key Laboratory of Joint Degeneration and Injury ChangshaHunan410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan410008China Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment Ministry of EducationXiangya HospitalCentral South UniversityChangshaChina

Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction;however,the effects on skeletal tissue and the underlying mechanisms are still ***,we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles,leading to a switch in skeletal stem/progenitor cell(SSPC)differentiation between osteoblasts and adipocytes and bone *** marrow macrophage(BMM)-secreted extracellular vesicles(BMM-EVs)from obese mice induced bone deterioration(decreased bone volume,bone microstructural deterioration,and increased adipocyte numbers)when administered to lean ***,BMM-EVs from lean mice rejuvenated bone deterioration in obese *** further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates,miR-140(with the function of promoting adipogenesis)and miR-378a(with the function of enhancing osteogenesis)coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 *** miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration,while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean *** miR-378a conditional depletion in mice led to obesity-like bone *** importantly,we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system,and this approach rescued bone deterioration in obese ***,our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.

关键词： Obesity-induced bone deterioration Macrophage-derived extracellular vesicles Skeletal stem/progenitor cells cell fate Aptamer cell-specific targeting

The second polar body contributes to the fate asymmetry in the mouse embryo

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National Science Review 2022年第7期9卷 32-42页

作者： Hongbin Jin Yang Han Huasong Wang J.Xiao He Li Weimin Shen Lin Zhang Luxi Chen Shunji Jia Ping Yuan Hui Chen Anming Meng Laboratory of Molecular Developmental Biology State Key Laboratory of Membrane BiologyTsinghua-Peking Center for Life Sciences School of Life SciencesTsinghua University Center for Reproductive Genetics and Reproductive Medicine Sun Yat-sen Memorial HospitalSun Yat-sen University Guangzhou Laboratory

The polar bodies(PBs) are extruded microcells during oocyte meiosis and generally regarded as inessentials for embryonic ***,PBs have been widelyused as important materials for pre-implantation genetic diagnosis in *** we report that the second PB(PB2) in the mouse zygote may play roles in cell-fate specification and post-implantation development.A subset of mRNAs encoding pluripotency-related factors are enriched in *** proteins maybe synthesized in PB2 after fertilization and transport from PB2 to the zygote before the two-cell *** PB2-attached blastomere(pbB) at the two-cell stage,compared to the other blastomere(npbB),likely contributes more descendants to the inner cell mass(ICM) lineage in the *** of PB2 from the zygote or transient blockage of material exchange between PB2 and the zygote by nocodazole treatment appears to cause a loss of the ICM fate bias of ***2 removal or nocodazole treatment also results in abnormal post-implantation *** of PB2 lysate into pbB of PB2-removed two-cell-stage embryos may reset the cell-fate preference and rescue post-implantation *** data collectively suggest that PB2 would demarcate the earliest cell-fate asymmetry of the mouse zygote and be required for post-implantation development.

关键词： mouse embryo polar body cell fate asymmetry

Steering Against Wind： A New Network of NamiRNAs and Enhancers

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Genomics, Proteomics & Bioinformatics 2017年第5期15卷 331-337页

作者： ying liang qingping zou wenqiang yu Laboratory of RNA Epigenetics.Institutes of Biomedical Sciences&Department of General Surgery Huashan Hospital Cancer M etastasis Institute Fudan UniversityShanghai 200032China Department of Biochemistry and Molecular Biology Shanghai Medical College MOE Key Laboratory of Metabolism and Molecular MedicineDepartment of Molecular BiologyFudan UniversityShanghai 200032China Collaborative Innovation Center for Genetics and Development School of Life SciencesFudan UniversityShanghai 200433China

MicroRNAs （miRNAs） are a class of endogenous non-coding RNAs with regulatory functions. Traditionally, miRNAs are thought to play a negative regulatory role in the cytoplasm by binding to the YUTR of target genes to degrade mRNA or inhibit translation. However, it remains a challenge to interpret the potential function of many miRNAs located in the nucleus. Recently, we reported a new type of miRNAs present in the nucleus, which can activate gene expres- sion by binding to the enhancer, and named them nuclear activating miRNAs （NamiRNAs）. The discovery of NamiRNAs showcases a complementary regulatory mechanism of miRNA, demon- strating their differential roles in the nucleus and cytoplasm. Here, we reviewed miRNAs in nucleus to better understand the function of NamiRNAs in their interactions with the enhancers. Accord- ingly, we propose a NamiRNA--enhancer-target gene activation network model to better under- stand the crosstalk between NamiRNAs and enhancers in regulating gene transcription. Moreover, we hypothesize that NamiRNAs may be involved in cell identity or cell fate determina- tion during development, although further study is needed to elucidate the underlying mechanisms in detail.

关键词： Nuclear activating miRNAs Tissue-specific enhancers Transcriptional gene activa-tion cell identity cell fate