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

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 transitions.From 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 sites.The development and maintenance of hematopoietic lineages are orchestrated by cell-intrinsic gene regulatory networks and cell-extrinsic microenvironmental cues.Owing 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 provided.Here,we review the evolving views of HSPC biology during developmental and postnatal hematopoiesis.Moreover,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

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A phase separation-fortified bi-specific adaptor for conditional tumor killing

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Science China(Life Sciences) 2024年第7期67卷 1385-1397页

作者： Yuyan Liu Yuting Zhu Weifan Xu Pilong Li State Key laboratory of membrane biology Frontier Research Center for Biological StructureTsinghua University-Peking University Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China

A common approach in therapeutic protein development involves employing synthetic ligands with multivalency,enabling sophisticated control of signal transduction.Leveraging the emerging concept of liquid-liquid phase separation(LLPS)and its ability to organize cell surface receptors into functional compartments,we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways,thus inducing the rapid,potent,and specific apoptosis of tumor cells.Despite their simplicity,these“triggers”,named phase-separated Tumor Killers(hereafter referred to as psTK),are sufficient to yield interreceptor clustering of death receptors(represented by DR5)and tumor-associated receptors,with notable features:LLPSmediated robust high-order organization,well-choreographed conditional activation,and broad-spectrum capacity to potently induce apoptosis in tumor cells.The development of novel therapeutic proteins with phase-separation modalities showcases the power of spatially reorganizing signal transduction.This approach facilitates the diversification of cell fate and holds promising potential for targeted therapies against challenging tumors.

关键词： phase separation therapeutic proteins receptor-ligand interactions DR5 tumor apoptosis

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Porous metal oxides in the role of electrochemical CO_(2) reduction reaction

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Journal of Energy Chemistry 2024年第1期88卷 373-398,I0009页

作者： Ziqi Zhang Jinyun Xu Yu Zhang Liping Zhao Ming Li Guoqiang Zhong Di Zhao Minjing Li Xudong Hu Wenju Zhu Chunming Zheng Xiaohong Sun School of Chemical Engineering and Technology Tianjin Key Laboratory of Green Chemical Technology and Process EngineeringState Key Laboratory of Separation Membrane and Membrane ProcessesTiangong UniversityTianjin 300387China School of Materials Science and Engineering Key Laboratory of Advanced Ceramics and Machining TechnologyMinistry of EducationTianjin UniversityTianjin 300072China

The global energy-related CO_(2) emissions have rapidly increased as the world economy heavily relied on fossil fuels.This paper explores the pressing challenge of CO_(2) emissions and highlights the role of porous metal oxide materials in the electrocatalytic reduction of CO_(2)(CO_(2)RR).The focus is on the development of robust and selective catalysts,particularly metal and metal-oxide-based materials.Porous metal oxides offer high surface area,enhancing the accessibility to active sites and improving reaction kinetics.The tunability of these materials allows for tailored catalytic behavior,targeting optimized reaction mechanisms for CO_(2)RR.The work also discusses the various synthesis strategies and identifies key structural and compositional features,addressing challenges like high overpotential,poor selectivity,and low stability.Based on these insights,we suggest avenues for future research on porous metal oxide materials for electrochemical CO_(2) reduction.

关键词： CO_(2)reduction Carbon dioxide Transformation Porous metal oxides Electrocatalysis

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Enhanced population of excited single state strategy:Irradiation and ultrasound dual-response and host tumor-driven nanosensitizers construction in triple synergistic therapy

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Nano Research 2024年第6期17卷 5501-5511页

作者： Yaning Li Mengyan Tian Tianyue Yang Jiayu Cao Hongli Chen Jun Guo Pai Liu Yi Liu State Key laboratory of Separation membranes and membrane Processes School of Materials Science and EngineeringTiangong UniversityTianjin 300387China State Key laboratory of Separation membranes and membrane Processes School of ChemistryTiangong UniversityTianjin 300387China State Key laboratory of Separation membranes and membrane Processes School of Life ScienceTiangong UniversityTianjin 300387China State Key laboratory of Separation membrane and membrane Process&Tianjin Key laboratory of Green Chemical Technology and Process Engineering School of ChemistryTiangong UniversityTianjin 300387China School of Chemical and Environmental Engineering Wuhan Polytechnic UniversityWuhan 430023China Cangzhou Institute of Tiangong University Cangzhou 061000China

Phototheranostics is an emerging field in synergistic antitumor therapy in which irradiation and sensitizers are combined to produce reactive oxygen species(ROS),bio-images,and high temperatures.All of these are arrived from the energy of sensitizers,which located in excited single state(S_(1)).Undeniably,the decentralization of the S_(1)population indirectly decreases the effect of each individual treatment.In this study,a strategy was proposed for enhancing the S_(1)population,and a sensitizer with mitochondrial targeting property,1,4-indolyl iodinated pyrrolo[3,2-b]pyrrole derivative(2I-TPIS),was assembled into adenosine triphosphate(ATP)-responsive nanoparticles(DPA-2I NPs)to achieve dual responses to irradiation and ultrasonication(US)for application to photo-sonodynamic therapy(PSDT).Compared with monotherapies,2I-TPIS generated more ROS in PSDT,inducing mitochondrial autophagy and apoptosis,which in turn triggered immunogenic cell death(ICD).Subsequently,DPA-2I NPs were constructed and self-assembled with the chemotherapeutic agents DPA-Cd and 2I-TPIS to achieve a triple synergistic strategy involving chemotherapy(CT)and PSDT.DPA-2I NPs exhibited absolute sensitization,intra-tumoral overexpression of ATP,and disassembly.Importantly,the biosafety and potent antitumor efficiency of the DPA-2I NP-based“PSDT+CT”therapy were revealed using a 4T1 tumor model.The study results provide insights into the design of sensitizers possessing a sufficient S_(1)population and a highly efficient tumor ablation capacity derived from molecular structural modulation,further enabling triple synergistic antitumor therapies,and expanding the clinical application of sensitizers.

关键词： triphosphate(ATP)-activated nano-sensitizers photo-sonodynamic therapy aggregation-induced emission enhanced excited state population

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An optimized method of culturing neurons based on polyacrylamide gel

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Biophysics Reports 2024年第1期10卷 41-47页

作者： Yongjing Qiao Jihong Gong Ziqi Jin Yiting Tu Xiaofei Yang Key laboratory of Cognitive Science Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis & Treatment Laboratory of Membrane Ion Channels and Medicine College of Biomedical Engineering SouthCentral Minzu University

Substrate stiffness is a microenvironment with a certain stiffness constructed by the extracellular matrix and adjacent cells, which plays an important role in the growth and development of cells and tissue formation. Studies have indicated that the stiffness of the brain is about 0.1–1 kPa. The physiological and pathological processes of the nervous system are mediated by the substrate stiffness that the neurons suffer. However, how substrate stiffness regulates these processes remains to be studied. Culturing neurons on substrates with different stiffness in vitro is one of the best methods to study the role of stiffness in regulating neuronal development and activity. In this study, by changing the preparation time and the activation time of polyacrylamide gel, we provide an improved method that achieves a low toxic substrate environment for better primary neuron adhesion and development. Hope that this method is convenient for those studying the role of substrate stiffness in neurons.

关键词： Polyacrylamide gel Neuron culture Cell adhesion Neural cell development

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A commentary of“Initial DNA melting in human DNA replication initiation”:Top 10 Scientific Advances of 2023,China

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Fundamental Research 2024年第3期4卷 701-703页

作者： Ningning Li Ning Gao State Key laboratory of membrane biology Peking-Tsinghua Center for Life SciencesSchool of Life SciencesPeking UniversityBeijing 100871China

DNA replication is a complicated process involving several dozens of factors.The molecular machine of eukaryotic DNA replication,replisome,consists of at least three essential modules:one replicative DNA helicase CMG(Cdc45-MCM-GINS)and two sets of DNA polymerase complexes responsible for the synthesis of the leading and lagging strands,respectively.As the core of CMG,MCM is a ring-shaped helicase motor composed of six homologous AAA+ATPase subunits,Mcm2 to Mcm7.The human genome is enormous,with over 3 billion base pairs.To efficiently duplicate the entire genome within a limited time,DNA replication is initiated from more than 25,000 discrete sites simultaneously.

关键词： DNA initiated shaped

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Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis laboratory of Developmental biology Department of Biology University of Patras laboratory of Cellular and Molecular Neurobiology-Stem Cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson’s disease substantia

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Electrostatic and hydrophobic interaction cooperative nanochaperone regulates protein folding

Aggregate

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Aggregate 2024年第1期5卷 419-426页

作者： Xiaohui Wu Fei Deng Yujie Chen Mengchen Xu Feihe Ma Linqi Shi Key laboratory of Functional Polymer Materials of Ministry of Education State Key Laboratory of Medicinal Chemical BiologyInstitute of Polymer Chemistry and College of ChemistryNankai UniversityTianjinP.R.China School of Materials Science and Engineering and State Key laboratory of Separation membranes and membrane Processes Tiangong UniversityTianjinP.R.China

Natural molecular chaperones utilize spatially ordered multiple molecular forces to effectively regulate protein folding.However,synthesis of such molecules is a big challenge.The concept of“aggregate science”provides insights to construct chemical entities(aggregates)beyond molecular levels to mimic both the structure and function of natural chaperone.Inspired by this concept,herein we fabricate a novel multi-interaction(i.e.,electrostatic and hydrophobic interaction)cooperative nanochaperone(multi-co-nChap)to regulating protein folding.This multi-co-nChap is fabricated by rationally introducing electrostatic interactions to the surface(corona)and confined hydrophobic microdomains(shell)of traditional single-hydrophobic interaction nanochaperone.We demonstrate that the corona electrostatic attraction facilitates the diffusion of clients into the hydrophobic microdomains,while the shell electrostatic interaction balances the capture and release of clients.By finely synergizing corona electrostatic attraction with shell electrostatic repulsion and hydrophobic interaction,the optimized multi-co-nChap effectively facilitated de novo folding of nascent polypeptides.Moreover,the synergy between corona electrostatic attraction,shell electrostatic attraction and shell hydrophobic interaction significantly enhanced the capability of multi-co-nChap to protect native proteins from denaturation at harsh temperatures.This work provides important insights for understanding and design of nanochaperone,which is a kind of ordered aggregate with chaperone-like activity that beyond the level of single molecule.

关键词： chaperone-like activity cooperative effect nanochaperones ordered aggregates protein folding

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Stay in touch with the endoplasmic reticulum

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Science China(Life Sciences) 2024年第2期67卷 230-257页

作者： Sha Sun Gan Zhao Mingkang Jia Qing Jiang Shulin Li Haibin Wang Wenjing Li Yunyun Wang Xin Bian Yan G.Zhao Xun Huang Ge Yang Huaqing Cai Jose C.Pastor-Pareja Liang Ge Chuanmao Zhang Junjie Hu National laboratory of Biomacromolecules Institute of BiophysicsUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China The Ministry of Education Key laboratory of Cell Proliferation and Differentiation College of Life SciencesPeking UniversityBeijing 100871China State Key laboratory of membrane biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China laboratory of Computational biology&Machine Intelligence School of Artificial IntelligenceUniversity of Chinese Academy of SciencesBeijing 100049China State Key laboratory of Medicinal Chemical biology College of Life SciencesNankai UniversityTianjin 300071China Brain Research Center Department of BiologySchool of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China State Key laboratory of Molecular Developmental biology Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China Institute of Neurosciences Consejo Superior de Investigaciones Científicas-Universidad Miguel HernándezSan Juan de Alicante 03550Spain

The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic cells.As a result,it engages a variety of organelles by establishing membrane contact sites(MCSs).These contacts regulate organelle positioning and remodeling,including fusion and fission,facilitate precise lipid exchange,and couple vital signaling events.Here,we systematically review recent advances and converging themes on ER-involved organellar contact.The molecular basis,cellular influence,and potential physiological functions for ER/nuclear envelope contacts with mitochondria,Golgi,endosomes,lysosomes,lipid droplets,autophagosomes,and plasma membrane are summarized.

关键词： endoplasmic reticulum nuclear envelope mitochondria Golgi apparatus endosome lysosome lipid droplets autophagosome plasma membrane membrane contact site

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JA-mediated MYC2/LOX/AOS feedback loop regulates osmotic stress response in tea plant

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Horticultural Plant Journal 2024年第3期10卷 931-946页

作者： Junyan Zhu Hongrong Chen Lu Liu Xiaobo Xia Xiaomei Yan Xiaozeng Mi Shengrui Liu Chaoling Wei State Key laboratory of Tea Plant biology and Utilization/Key laboratory of Tea biology and Tea Processing of Ministry of Agriculture/Anhui Provincial laboratory of Tea Plant biology and Utilization Anhui Agricultural UniversityHefeiAnhui 230036China

Osmotic stress caused by low-temperature,drought and salinity was a prevalent abiotic stress in plant that severely inhibited plant development and agricultural yield,particularly in tea plant.Jasmonic acid(JA)is an important phytohormone involving in plant stress.However,underlying molecular mechanisms of JA modulated osmotic stress response remains unclear.In this study,high concentration of mannitol induced JA accumulation and increase of peroxidase activity in tea plant.Integrated transcriptome mined a JA signaling master,MYC2 transcription factor is shown as a hub regulator that induced by mannitol,expression of which positively correlated with JA biosynthetic genes(LOX and AOS)and peroxidase genes(PER).CsMYC2 was determined as a nuclei-localized transcription activator,furthermore,ProteinDNA interaction analysis indicated that CsMYC2 was positive regulator that activated the transcription of CsLOX7,CsAOS2,CsPER1 and CsPER3via bound with their promoters,respectively.Suppression of CsMYC2 expression resulted in a reduced JA content and peroxidase activity and osmotic stress tolerance of tea plant.Overexpression of CsMYC2 in Arabidopsis improved JA content,peroxidase activity and plants tolerance against mannitol stress.Together,we proposed a positive feedback loop mediated by CsMYC2,CsLOX7 and CsAOS2 which constituted to increase the tolerance of osmotic stress through fine-tuning the accumulation of JA levels and increase of POD activity in tea plant.

关键词： Camellia sinensis Jasmonic acid(JA) MYC2 transcription factor Lipoxygenase(LOX) Osmotic stress Peroxidase(POD) Reactive oxygen species(ROS)

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