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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

Opto-fluidically multiplexed assembly and micro-robotics

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Light(Science & Applications) 2024年第3期13卷 544-554页

作者： Elena Erben Weida Liao Antonio Minopoli Nicola Maghelli Eric Lauga Moritz Kreysing Max Planck institute of Molecular Cell biology and Genetics Dresden 01307Germany Center for systems biology Dresden 01307Germany institute of Biological and Chemical systems–Biological Information Processing.Karlsruhe institute of Technology(KIT) Eggenstein-Leopoldshafen 76344Germany Department of Applied Mathematics and Theoretical Physics University of CambridgeCambridge CB30WAUK

Techniques for high-definition micromanipulations,such as optical tweezers,hold substantial interest across a wide range of ***,their applicability remains constrained by material properties and laser *** while microfluidic manipulations have been suggested as an alternative,their inherent capabilities are limited and further hindered by practical challenges of implementation and *** we show that the iterative application of laser-induced,localized flow fields can be used for the relative positioning of multiple micro-particles,irrespectively of their material *** to the standing theoretical proposal,our method keeps particles mobile,and we show that their precision manipulation is non-linearly accelerated via the multiplexing of temperature stimuli below the heat diffusion *** resulting flow fields are topologically rich and mathematically *** represent unprecedented microfluidic control capabilities that are illustrated by the actuation of humanoid micro-robots with up to 30 degrees of freedom,whose motions are sufficiently well-defined to reliably communicate personal characteristics such as gender,happiness and *** results constitute high-definition micro-fluidic manipulations with transformative potential for assembly,micro-manufacturing,the life sciences,robotics and optohydraulically actuated micro-factories.

关键词： manipulation fluid assembly

Inter-chromosomal insertions into wild-type chromosomes induced by SCRaMbLE

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Frontiers of Chemical Science and Engineering 2024年第9期18卷 125-135页

作者： Sijie Zhou Junyanrui Li Xichen Cui Ying Wang Ying-Jin Yuan Frontiers Science Center for Synthetic biology and Key Laboratory of systems Bioengineering(Ministry of Education) School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300072China Frontiers Research institute for Synthetic biology Tianjin UniversityTianjin 300072China

Genomic rearrangements play a crucial role in shaping biological phenotypic diversity and driving species *** chromosome rearrangement and modification by LoxP-mediated evolution(SCRaMbLE)has been applied to explore large-scale genomic rearrangements,yet it has been observed that these rearrangements occur exclusively in genomic regions containing loxPsym ***,we found that SCRaMbLE of synthetic yeast harboring synthetic chromosome V and X can generate a variety of synthetic segment insertions into wild-type chromosomes,ranging from 1 to 300 ***,it was revealed that the novel insertions impacted the transcriptional level of neighboring regions and affected the production of exemplar pathway of ***,our results improve the understanding of the ability of SCRaMbLE to generate complex structural variations in nonsynthetic regions and provide a potential model to explore genomic transposable events.

关键词： genomic rearrangements synthetic yeast genome SCRaMbLE inter-chromosomal insertions synthetic biology

A zebrafish tufm mutant model for the COXPD4 syndrome of aberrant mitochondrial function

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Journal of Genetics and Genomics 2024年第9期51卷 922-933页

作者： Ting Li Tursunjan Aziz Guangyuan Li Lin Zhang Jihua Yao Shunji Jia School of Life Sciences Fudan UniversityShanghai 200438China State Key Laboratory of membrane biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China State Key Laboratory of Molecular Developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Mitochondrial dysfunction is a critical factor leading to a wide range of clinically heterogeneous and often severe disorders due to its central role in generating cellular *** in the TUFM gene are known to cause combined oxidative phosphorylation deficiency 4(COXPD4),a rare mitochondrial disorder characterized by a comprehensive quantitative deficiency in mitochondrial respiratory chain(MRC)*** development of a reliable animal model for COXPD4 is crucial for elucidating the roles and mechanisms of TUFM in disease pathogenesis and benefiting its medical *** this study,we construct a zebrafish tufm−/−mutant that closely resembles the COXPD4 syndrome,exhibiting compromised mitochondrial protein translation,dysfunctional mitochondria with oxidative phosphorylation defects,and significant metabolic suppression of the tricarboxylic acid *** this COXPD4 zebrafish model,we comprehensively validate the clinical relevance of TUFM mutations and identify probucol as a promising therapeutic approach for managing *** data offer valuable insights for understanding mitochondrial diseases and developing effective treatments.

关键词： Tufm Mitochondria COXPD4 Disease model Zebrafish

Identification of crucial roles of transcription factor IhfA on high production of free fatty acids in Escherichia coli

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Synthetic and systems Biotechnology 2024年第1期9卷 144-151页

作者： Lixia Fang Ziyi Han Xueru Feng Xueyan Hao Mengxiao Liu Hao Song Yingxiu Cao Frontiers Science Center for Synthetic biology and Key Laboratory of systems Bioengineering(Ministry of Education) School of Chemical Engineering and TechnologyTianjin UniversityTianjin300072China Frontiers Research institute for Synthetic biology Tianjin UniversityChina

Transcription factor engineering has unique advantages in improving the performance of microbial cell factories due to the global regulation of gene *** analyses and reverse engineering enable learning and subsequent incorporation of novel design strategies for further ***,we identify the role of the global regulator IhfA for overproduction of free fatty acids(FFAs)using CRISPRi-facilitated reverse engineering and cellular physiological *** the differentially expressed genes in the ihfAL􀀀strain,a total of 14 beneficial targets that enhance FFAs production by above 20% are identified,which involve membrane function,oxidative stress,and *** membrane-related genes,the engineered strains obtain lower cell surface hydrophobicity and increased average length of membrane lipid *** oxidative stress-related genes,the engineered strains present decreased reactive oxygen species(ROS)*** gene modulations enhance cellular robustness and save cellular resources,contributing to FFAs *** study provides novel targets and strategies for engineering microbial cell factories with improved FFAs bioproduction.

关键词： Free fatty acids CRISPRi ihfA Cell membrane ROS

Aagab is required for zebrafish larval development by regulating neural activity

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Journal of Genetics and Genomics 2024年第6期51卷 630-641页

作者： Shihui Ding Tursunjan Aziz Anming Meng Shunji Jia State Key Laboratory of membrane biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China Guangzhou Laboratory GuangzhouGuangdong 510320China State Key Laboratory of Molecular Developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Clathrin-mediated endocytosis has been implicated in various physiological processes,including nutrient uptake,signal transduction,synaptic vesicle recycling,maintenance of cell polarity,and antigen *** prior knowledge of its importance as a key regulator in promoting clathrin-mediated endocytosis,the physiological function of α-and γ-adaptin binding protein(aagab)remains *** this study,we investigate the biological function of aagab during zebrafish *** establish a loss-of-function mutant of aagab in zebrafish,revealing impaired swimming and early larval *** the high expression level of aagab in the brain,we probe into its physiological role in the nervous *** mutants display subdued calcium responses and local field potential in the optic tectal neurons,aligning with reduced neurotransmitter release(e.g.,norepinephrine)in the tectal neuropil of aagab *** aagab mRNA or nervous stimulant treatment in mutants restores neurotransmitter release,calcium responses,swimming ability,and ***,our observations show delayed release of FM 1-43 in AAGAB knockdown differentiated neuroblastoma cells,pointing towards a probable link to defective clathrin-mediated synaptic vesicle *** conclusion,our study underscores the significance of Aagab in neurobiology and suggests its potential impacts on neurological disorders.

关键词： Aagab Endocytosis Neural activity Synaptic transmitter release Zebrafish

Identific tion of quantitative trait loci and associated candidate genes for pregnancy success in Angus–Brahman crossbred heifers

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Journal of Animal Science and Biotechnology 2024年第1期15卷 162-170页

作者： Quinn A.Hoorn Gabriel A.Zayas Eduardo E.Rodriguez Laura M.Jensen Raluca G.Mateescu Peter J.Hansen Department of Animal Sciences Donald Henry Barron Reproductive and Perinatal Biology Research Programand the Genetics InstituteUniversity of FloridaGainesvilleFLUSA School of Applied systems biology La Trobe UniversityBundooraVIC 3083Australia

Background In beef cattle, more than 50% of the energy input to produce a unit of beef is consumed by the female that produced the calf. Development of genomic tools to identify females with high genetic merit for reproductive function could increase the profitability and sustainability of beef *** Genome-wide association studies(GWAS) were performed using a single-step genomic best linear unbiased prediction approach on pregnancy outcome traits from a population of Angus–Brahman crossbred heifers. Furthermore, a validation GWAS was performed using data from another farm. Heifers were genotyped with the Bovine GGP F250 array that contains 221,077 SNPs. In the discovery population, heifers were bred in winter breeding seasons involving a single round of timed artificial insemination(AI) followed by natural mating for 3 months. Two phenotypes were analyzed: pregnancy outcome to first-service AI(PAI;n = 1,481) and pregnancy status at the end of the breeding season(PEBS;n = 1,725). The heritability was estimated as 0.149 and 0.122 for PAI and PEBS, respectively. In the PAI model, one quantitative trait locus(QTL), located between 52.3 and 52.5 Mb on BTA7, explained about 3% of the genetic variation, in a region containing a cluster of γ-protocadherin genes and SLC25A2. Other QTLs explaining between 0.5% and 1% of the genetic variation were found on BTA12 and 25. In the PEBS model, a large QTL on BTA7 was synonymous with the QTL for PAI, with minor QTLs located on BTA5, 9, 10, 11, 19, and 20. The validation population for pregnancy status at the end of the breeding season were Angus–Brahman crossbred heifers bred by natural mating. In concordance with the discovery population, the large QTL on BTA7 and QTLs on BTA10 and 12 were *** In summary, QTLs and candidate SNPs identified were associated with pregnancy outcomes in beef heifers, including a large QTL associated with a group of protocadherin genes. Confirmation of these associations

关键词： Beef cattle Fertility GWAS QTL

An efficient and safe strategy for germ cell-specific automatic excision of foreign DNA in F1 hybrid transgenic silkworms

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Insect Science 2024年第1期31卷 28-46页

作者： Dingpei Long Rongpeng Liu Yang Huang Anyao Fu Yuli Zhang Zhanzhang Hao Qiang Li Hanfu Xu Zhonghuai Xiang Aichun Zhao State Key Laboratory of Resource Insects Institute of Sericulture and Systems BiologySouthwest UniversityChongqingChina Department of biology Georgia State UniversityAtlantaGeorgiaUSA Guangxi institute of Sericulture Science NanningGuangxiChina Department of Mathematics and Statistics Georgia State UniversityAtlantaGeorgiaUSA

The safety of transgenic technology is a major obstacle in the popularization and use of transgenic silkworms and their *** sericulture,only the first filial generation(F1)hybrid eggs produced by cross-breeding Japanese and Chinese original strains are usually used for the large-scale breeding of silkworms,but this may result in uncontrolled transgene dispersal during the popularization and application of the F1 hybrid transgenic *** address this issue,we developed a safe and efficient strategy using the GAL4/Upstream activating sequence(UAS)system,the FLP/flippase recognition target(FRT)system,and the gonad-specific expression gene promoters(RSHP1p and Nanosp)for the germ cell-specific automatic excision of foreign DNA in the F1 hybrid transgenic *** established 2 types of activator strains,R1p::GAL4-Gr and Nsp::GAL4-Gr,containing the testis-specific GAL4 gene expression cassettes driven by RSHP1p or Nanosp,respectively,and 1 type of effector strain,UAS::FLP-Rg,containing the UAS-linked FLP gene expression *** FLP recombinase-mediated sperm-specific complete excision of FRT-flanked target DNA in the F1 double-transgenic silkworms resulting from the hybridization of R1p::GAL4-Gr and UAS::FLP-Rg was 100%,whereas the complete excision efficiency resulting from the hybridization of Nsp::GAL4-Gr and UAS::FLP-Rg ranged from 13.73%to 80.3%.Additionally,we identified a gene,sw11114,that is expressed in both testis and ovary of Bombyx mori,and can be used to establish novel gonad-specific expression systems in transgenic *** strategy has the potential to fundamentally solve the safety issue in the production of F1 transgenic silkworm eggs and provides an important reference for the safety of transgenic technology in other insect species.

关键词： Bombyx mori FLP/FRT system GAL4/UAS system germ cell-specific excision safety of transgenic technology transgenic silkworm

Application of plant DNA metabarcoding of lake sediments for monitoring vegetation compositions on the Tibetan Plateau

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Science China Earth Sciences 2024年第11期67卷 3594-3609页

作者： Kai WU Kai LI Weihan JIA Kathleen R.STOOF-LEICHSENRING Ulrike HERZSCHUH Jian NI Mengna LIAO Fang TIAN College of Life Sciences Zhejiang Normal University Polar Terrestrial Environmental systems Research Group Alfred Wegener Institute Helmholtz Centre for Polar and Marine Research institute of Environmental Science and Geography University of Potsdam institute of Biochemistry and biology University of Potsdam College of Resource Environment and Tourism Capital Normal University

Benefiting from the rapid development of environmental DNA(eDNA) technologies, sedimentary DNA(sedDNA)emerges as a promising tool for monitoring plant compositions in remote regions. The Tibetan Plateau(TP), renowned for its harsh environment and numerous ponds and lakes, presents a potentially demanding region for the application of sedDNA on vegetation investigations. Here, we used the g and h universal primers for the P6 loop region of the chloroplast trn L(UAA)intron to amplify plant DNA in surface sediments from 59 ponds and small lakes on the southwestern TP. The applicability and limitations of using plant DNA metabarcoding for modern vegetation monitoring and palaeo-vegetation reconstructions have been assessed by comparing sedDNA, pollen, and vegetation survey data. Our results showed that plant DNA metabarcoding recorded 186 terrestrial taxa, of which 30.1% can be identified at the species level. The plant sedDNA approach can effectively disclose the dominant plant taxa(including Asteraceae, Cyperaceae and Poaceae) and significant vegetation assemblages in the vicinity of the investigated sites. The number of taxa and taxonomic resolution of plant sedDNA exceeded that of pollen analysis(75 taxa detected, 5.3% can be identified at species level). Unlike pollen that retains a broad spectrum of regional plant signals(including Pinus and Artemisia), plant sedDNA mirrors very local plants, underscoring its utility in local vegetation monitoring and reconstructions. To conclude, plant DNA metabarcoding of(small) lake sediments warrant increased attention in the future for local vegetation monitoring and reconstructions on the TP.

关键词： Sedimentary DNA (sedDNA) Metabarcoding Pollen Vegetation composition Tibetan Plateau