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Outcomes of haploidentical bone marrow transplantation in patients with severe aplastic anemia-II that progressed from non-severe acquired aplastic anemia

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Frontiers of Medicine 2021年第5期15卷 718-727页

作者： Hongchen Liu Xiaoli Zheng Chengtao Zhang Jiajun Xie Beibei Gao Jing Shao Yan Yang Hengxiang Wang Jinsong Yan department of Hematology Liaoning Medical Center for Hematopoietic Stem Cell TransplantationDalian Key Laboratory of HematologyLiaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational MedicineDiamond Bay Institute of Hematologythe Second Hospital of Dalian Medical UniversityDalian 116027China department of Hematology Air Force Medical CenterPLABeijing 100142China department of Environmental Health and Toxicology Liaoning Medical Center for Hematopoietic Stem Cell TransplantationLiaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational MedicineSchool of Public HealthDalian Medical UniversityDalian 116044China

Severe aplastic anemia II(SAA-II)progresses from non-severe aplastic anemia(NSAA).The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation(haplo-BMT)in patients lacking a human leukocyte antigen(HLA)-matched *** study aimed to investigate the efficacy of haplo-BMT for patients with ***-two patients were included and followed up,and FLU/BU/CY/ATG was used as conditioning *** these patients,21 were successfully engrafted,19 of whom survived after *** patients experienced grade II–IV aGvHD,including two with grade III–IV *** patients experienced chronic GvHD,among whom four were mild and two were *** patients experienced infections during *** was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease,and both recovered after rituximab ***-BMT achieved 3-year overall survival and disease-free survival rate of 86.4%±0.73%after a median follow-up of 42 months,indicating its effectiveness as a salvage *** promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.

关键词： severe aplastic anemia non-severe acquired aplastic anemia haploidentical bone marrow transplantation outcomes

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Epigenetic control on cell fate choice in neural stem cells

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Protein & cell 2012年第4期3卷 278-290页

作者： Xiao-Ling Hu Yuping Wang Qin Shen center for stem cell biology and Regenerative Medicine School of MedicineTsinghua Center for Life SciencesTsinghua UniversityBeijing 100084China department of Pharmacy Tianjin Children’s HospitalTianjin 300074China

Derived from neural stem cells(NSCs)and progenitor cells originated from the neuroectoderm,the nervous system presents an unprecedented degree of cellular diversity,interwoven to ensure correct connections for propagating information and responding to environ-mental *** and progenitor cells must integrate cell-intrinsic programs and environmental cues to achieve production of appropriate types of neurons and glia at appropriate times and places during *** developmental dynamics are reflected in changes in gene expression,which is regulated by transcription factors and at the epigenetic *** early commitment of neural lineage to functional plas-ticity in terminal differentiated neurons,epigenetic regulation is involved in every step of neural *** we focus on the recent advance in our un-derstanding of epigenetic regulation on orderly genera-tion of diverse neural cell types in the mammalian nervous system,an important aspect of neural devel-opment and regenerative medicine.

关键词： neural stem cells(NSCs) epigenetic regu-lation neurogenesis gliogenesis radial glial cell cerebral cortex subventricular zone(SVZ) DNA methylation histone modification

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MicroRNA-125b Accelerates and Promotes PML-RARa-driven Murine Acute Promyelocytic Leukemia

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Biomedical and Environmental Sciences 2022年第6期35卷 485-493页

作者： GUO Bo QIN Ran CHEN Ji Jun PAN Wen LU Xue Chun department of Hematology The Second Medical Centre&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China department of Genetics Yale University School of MedicineNew HavenConnecticut 06510USA yale stem cell center Yale Cancer CenterNew HavenCT06520USA

Objective Most acute promyelocytic leukemia cases are characterized by the PML-RARa fusion oncogene and low white cell counts in peripheral *** Based on the frequent overexpression of miR-125-family miRNAs in acute promyelocytic leukemia,we examined the consequence of this phenomenon by using an inducible mouse model overexpressing human *** MiR-125b expression significantly accelerates PML-RARa-induced leukemogenesis,with the resultant induced leukemia being partially dependent on continued miR-125b ***,miR-125b expression led to low peripheral white cell counts to bone marrow blast percentage ratio,confirming the clinical observation in acute promyelocytic leukemia *** This study suggests that dysregulated miR-125b expression is actively involved in disease progression and pathophysiology of acute promyelocytic leukemia,indicating that targeting miR-125b may represent a new therapeutic option for acute promyelocytic leukemia.

关键词： miR-125b PML-RARA White blood cell Bone marrow blast

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Revolutionizing genetic disease treatment: The case of exagamglogene autotemcel

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The Innovation 2024年第3期5卷 5-6页

作者： Shuquan Rao Yao Yao Wenxuan Huo Yang Cao Lihua E.Budde State Key Laboratory of Experimental Hematology Institute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020 China 2Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing 100044 China 3Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies Chinese Academy of Medical Sciences(2019RU029)Beijing 100044 China 4department of Hematology&Cancer biology Research center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030 China 5department of Hematology&Hematopoietic stem cell Transplantation City of Hope National Medical CenterDuarteCA 91010USA

Recent approval of exagamglogene autotemcel(exa-cel)on November 16,2023,in the United Kingdom,developed by Vertex Pharmaceuticals and CRISPR Therapeutics,represents the first cell-based therapy for treatment of sickle cell disease(SCD)with recurrent vaso-occlusive crises(VOCs)or transfusion-dependentβ-thalassemia(TDT)in patients aged 12 and *** suit,the US Food and Drug Administration authorized exa-cel for the same indications on December 8,***-cel represents the first commercially approved CRISPR-based gene therapy,offering hope to approximately 25,000 eligible patients in the US and *** significance of exa-cel extends beyond revolutionizing therapeutic intervention in genetic medicine;it also raises profound ethical considerations and societal implications related to genome manipulation.

关键词： transfusion treatment manipulation

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Efficient derivation of embryonic stem cells from NOD-scid ll2rg-/-mice

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Protein & cell 2015年第12期6卷 916-918页

作者： Kang Liu Riguo Fang Haibo Li Weifeng Yang Zhenchuan Miao Jinhua Wen Hongkui Deng Peking University stem cell Research center Department of Cell Biology School of Basic Medical Sciences Peking University Health Science Center The MOE Key Laboratory of cell Proliferation and Differentiation College of Life Sciences Peking-Tsinghua Center for Life Sciences Peking University VITALSTAR Bitechnology Co. Ltd Shenzhen stem cell Engineering Laboratory Key Laboratory of Chemical Genomics Peking University Shenzhen Graduate School

Dear Editor,For decades,the stem cell field has pursued the development of humanized mice to further enhance our understanding of human hematopoiesis,innate immunity,infectious diseases,cancer biology and regenerative *** significant breakthrough in generating humanized mice was the development of NOD-scid ll2rg-/-mice,which are double homozygous for the severe combined immun-

关键词： Pluripotent stem cell Embryonic stem cell Line Severe Combine Immunodeficiency Humanize Mouse Humanize Mouse Model

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Integrative analysis of tumor stemness and immune microenvironment deciphers novel molecular subtypes in hepatocellular carcinoma

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Genes & Diseases 2024年第5期11卷 81-84页

作者： Zhiyi Wang Shuang Chen Dongxiao Li Hui Xu Siyuan Weng Yuyuan Zhang Yuqing Ren Chunguang Guo Xiuling Li Zaoqu Liu Xinwei Han department of Interventional Radiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China department of Gastroenterology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhouHenan 450004China center of Reproductive Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China department of Endovascular Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China State Key Laboratory of Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijing 102206China State Key Laboratory of Medical Molecular biology Institute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100730China

Hepatocellular carcinoma(HCC)is a highly heterogeneous tumor,with dynamic equilibrium and complex interplay between its intricate tumor nature and ambient tumor immune microenvironment(TIME).1 Elegant research has indicated that cancer stem cells,a small subset of neoplastic cells confined within dedicated niches,display stem cell-like properties and interact with cells in TIME,thereby imparting an indelible impact on stemness regulation,tumor heterogeneity,and cancer cell plasticity.2 Previous taxonomies solely from the perspective of stemness or TIME may introduce some degree of bias in the comprehension of HCC carcinogenesis,3,4 and thus it is of paramount importance to systematically consider tumor stemness and TIME as a whole to truly portray the biological landscape of HCC.

关键词： thereby landscape stem

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Intermittent compressive force induces cell cycling and reduces apoptosis in embryoid bodies of mouse induced pluripotent stem cells

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International Journal of Oral Science 2022年第1期14卷 40-50页

作者： Jeeranan Manokawinchoke Phoonsuk Limraksasin Hiroko Okawa Prasit Pavasant Hiroshi Egusa Thanaphum Osathanon Division of Molecular and Regenerative Prosthodontics Tohoku University Graduate School of DentistrySendaiMiyagiJapan Dental stem cell biology Research Unit and department of Anatomy Faculty of DentistryChulalongkorn UniversityBangkokThailand center for Advanced stem cell and Regenerative Research Tohoku University Graduate School of DentistrySendaiMiyagiJapan

In vitro manipulation of induced pluripotent stem cells(iPSCs) by environmental factors is of great interest for three-dimensional(3D) tissue/organ induction. The effects of mechanical force depend on many factors, including force and cell type. However,information on such effects in i PSCs is lacking. The aim of this study was to identify a molecular mechanism in i PSCs responding to intermittent compressive force(ICF) by analyzing the global gene expression profile. Embryoid bodies of mouse i PSCs, attached on a tissue culture plate in 3D form, were subjected to ICF in serum-free culture medium for 24 h. Gene ontology analyses for RNA sequencing data demonstrated that genes differentially regulated by ICF were mainly associated with metabolic processes,membrane and protein binding. Topology-based analysis demonstrated that ICF induced genes in cell cycle categories and downregulated genes associated with metabolic processes. The Kyoto Encyclopedia of Genes and Genomes database revealed differentially regulated genes related to the p53 signaling pathway and cell cycle. q PCR analysis demonstrated significant upregulation of Ccnd1, Cdk6 and Ccng1. Flow cytometry showed that ICF induced cell cycle and proliferation, while reducing the number of apoptotic cells. ICF also upregulated transforming growth factor β1(Tgfb1) at both m RNA and protein levels, and pretreatment with a TGF-β inhibitor(SB431542) prior to ICF abolished ICF-induced Ccnd1 and Cdk6 expression. Taken together,these findings show that TGF-β signaling in i PSCs enhances proliferation and decreases apoptosis in response to ICF, that could give rise to an efficient protocol to manipulate i PSCs for organoid fabrication.

关键词： cycling culture attached

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Gene positioning and genome function

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Frontiers in biology 2014年第4期9卷 255-268页

作者： Nidhi VISHNO Jie YAO department of cell biology Yale University School of Medicine New Haven CT 06520 USA

The eukaryotic genome is packaged as chromatin within the three-dimensional nuclear space. Decades of cytological studies have revealed that chromosomes and genes are non-randomly localized within the nucleus and such organizations have important roles on genome function. However, several fundamental questions remain to be resolved. For example, what is required for the preferential localization ofa gene to a nuclear landmark？ What is the mechanism underlying gene repositioning in the nucleus？ How does subnuclear gene positioning regulate gene transcription？ Recent studies have revealed that several factors such as DNA sequence composition, specific regulatory sequences, epigenetic modifications, chromatin remodelers, post-transcriptional regulators and nuclear architectural proteins can influence chromatin dynamics and gene positioning in a gene-specific manner among organisms from yeast to human. In this review, we discuss some recent findings as well as experimental tools to investigate subnuclear gene positioning and to explore its implications in genome functions.

关键词： nucleus transcription gene positioning epigenetics nuclear lamina chromatin

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An inducible CRISPR-ON system for controllable gene activation in human pluripotent stem cells

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Protein & cell 2017年第5期8卷 379-393页

作者： Jianying Guo Dacheng Ma Rujin Huang Jia Ming Min Ye Kehkooi Kee Zhen Xie Jie Na department of Basic Medical Sciences School of Medicine Center for Stem Cell Biology Tsinghua University Beijing 100084 China MOE Key Laboratory of Bioinformatics and Bioinformatics Division Center for Synthetic and System Biology TNLIST/ Department of Automation Tsinghua University Beijing 100084 China

Human pluripotent stem cells （hPSCs） are an important system to study early human development, model human diseases, and develop cell replacement therapies. However, genetic manipulation of hPSCs is challenging and a method to simultaneously activate multiple genomic sites in a controllable manner is sorely needed. Here, we constructed a *** system to efficiently upregulate endogenous genes in hPSCs. A doxycycline （Dox） inducible dCasg-VP64-p65-Rta （dCas9-VPR） transcription activator and a reverse Tet transactivator （rtTA） expression cassette were knocked into the two alleles of the AAVS1 locus to generate an iVPR hESC line. We showed that the dCas9-VPR level could be precisely and reversibly controlled by the addition and withdrawal of Dox. Upon transfection of multiplexed gRNA plasmid targeting the NANOG pro- moter and Dox induction, we were able to control NANOG gene expression from its endogenous locus. Interestingly, an elevated NANOG level promoted naive pluripotsnt gene expression, enhanced cell survival and clonogenicity, and enabled hESCs to integrate with the inner cell mass （ICM） of mouse blastocysts in vitro. Thus, iVPR cells provide a convenient platform for gene function studies as well as high-throughput screens in hPSCs.

关键词： CRISPR transcription activation humanpluripotent stem cells NANOG pluripotency

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Tipsy neural stem cells: chronic effects of alcohol on the brain

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Neural Regeneration Research 2019年第1期14卷 67-68页

作者： Caitlin R.Schlagal Ping Wu department of Neuroscience Cell Biology and Anatomy Center for Addiction Research University of Texas Medical Branch

Neurogenesis occurs in the adult brain and is defined as the production of new neurons from a population of cells known as neural stem cells(NSCs)(Ming and Song,2011).NSCs are also capable of self-renewal and differentiation into astrocytes or oligodendrocytes through processes known as astrogliogenesis and oligodendrogenesis,*** properties of NSCs are crucial not only during development,where they drive the formation of neural connections and brain growth,but also throughout life to generate new neurons and glia in several

关键词：神经干细胞大脑酒精星形细胞神经连接神经胶质神经发生神经原

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