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Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

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Signal Transduction and Targeted Therapy 2021年第11期6卷 3230-3245页

作者： Xia Li Mi Shao Xiangjun Zeng pengxu qian He Huang Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouPeople’s Republic of China Liangzhu Laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhou311121People’s Republic of China Institute of Hematology Zhejiang UniversityHangzhouZhejiangPeople’s Republic of China Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy HangzhouZhejiangPeople’s Republic of China Center of Stem Cell and Regenerative Medicine Zhejiang University School of MedicineHangzhouPeople’s Republic of China

Cytokine release syndrome(CRS)embodies a mixture of clinical manifestations,including elevated circulating cytokine levels,acute systemic inflammatory symptoms and secondary organ dysfunction,which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza,SARS-CoV and COVID-19,immunotherapy of tumor,after chimeric antigen receptor T(CAR-T)therapy,and in monogenic disorders and autoimmune ***,severe CRS is a very significant and life-threatening complication,which is clinically characterized by persistent high fever,hyperinflammation,and severe organ ***,CRS is a double-edged sword,which may be both helpful in controlling tumors/viruses/infections and harmful to the *** a high incidence and high levels of cytokines are features of CRS,the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain *** the present review,we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of *** that CRS is the major adverse event in human diseases and intervention therapy,our review delineates the characteristics,kinetics,signaling pathways,and potential mechanisms of CRS,which shows its clinical relevance for achieving both favorable efficacy and low toxicity.

关键词： cytokine release kinetics

Inflammation and aging:signaling pathways and intervention therapies

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3267-3295页

作者： Xia Li Chentao Li Wanying Zhang Yanan Wang pengxu qian He Huang Bone Marrow Transplantation Center the First Affiliated HospitalZhejiang University School of MedicineHangzhouPeople’s Republic of China Liangzhu Laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhou 311121China Institute of Hematology Zhejiang University&Zhejiang Engineering Laboratory for Stem Cell and ImmunotherapyHangzhou 310058China Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy Hangzhou 310058China Zhejiang UniversityUniversity of Edinburgh Institute Zhejiang University School of MedicineZhejiang UniversityHainingChina Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China

Aging is characterized by systemic chronic inflammation,which is accompanied by cellular senescence,immunosenescence,organ dysfunction,and age-related *** the multidimensional complexity of aging,there is an urgent ne... 详细信息

关键词： aging reduction dimensionality

SARS-CoV-2 N protein potentiates host NPM1-snoRNA translation machinery to enhance viral replication

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Signal Transduction and Targeted Therapy 2022年第11期7卷 4003-4006页

作者： Hui Wang Danrong Shi Penglei Jiang Zebin Yu Yingli Han Zhaoru Zhang Peihui Wang He Huang Hangping Yao pengxu qian Center of Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Liangzhu Laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhouChina Institute of Hematology Zhejiang University&Zhejiang Engineering Laboratory for Stem Cell and ImmunotherapyHangzhouChina School of Medicine Zhejiang UniversityHangzhouChina State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Advanced Medical Research Institute Cheeloo College of MedicineShandong UniversityJinanChina

Dear Editor,COVID-19(Coronavirus Disease 2019)is causing an unprecedented public health *** translation is crucial for virus ***(N)protein is among the most abundant SARS-CoV-2 proteins and highly conserved across cor... 详细信息

关键词： translation machinery among

Small noncoding RNAs play superior roles in maintaining hematopoietic stem cell homeostasis

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Blood Science 2022年第3期4卷 125-132页

作者： Hui Wang Wenchang qian Yingli Han pengxu qian Center of Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Liangzhu Laboratory Zhejiang University Medical CenterHangzhouChina Institute of Hematology Zhejiang University and Zhejiang Engineering Laboratory for Stem Cell and ImmunotherapyHangzhouChina

The maintenance of the mammalian blood system depends on hematopoietic stem cells(HSCs),which are a rare class of adult stem cells with self-renewal and multilineage differentiation *** homeostasis of hematopoietic stem cells is finely tuned by a variety of endogenous and exogenous regulatory factors,and disrupted balance will lead to hematological diseases including leukemia and ***,emerging studies have illustrated the cellular and molecular mechanisms underlying the regulation of HSC ***,the rapid development of second-generation sequencing technologies has uncovered that many small noncoding RNAs(ncRNAs)are highly expressed in HSCs,including snoRNAs,miRNAs,tsRNAs,circular RNAs,*** this study,we will summarize the essential roles and regulatory mechanisms of these small ncRNAs in maintaining HSC ***,this review provides up-to-date information in the regulation of HSC homeostasis by small ncRNAs,which sheds light into the development of therapeutic strategies against hematopoietic malignancies.

关键词： Hematopoietic stem cell Homeostasis Self-renewal Small noncoding RNAs

Generating hematopoietic cells from human pluripotent stem cells:approaches,progress and challenges

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Cell Regeneration 2023年第1期12卷 70-90页

作者： Haiqiong Zheng Yijin Chen qian Luo Jie Zhang Mengmeng Huang Yulin Xu Dawei Huo Wei Shan Ruxiu Tie Meng Zhang pengxu qian He Huang Bone Marrow Transplantation Center the First Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhou 310012China Liangzhu Laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhou 311121China Institute of Hematology Zhejiang UniversityHangzhou 310012China Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy Hangzhou 310012China Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China

Human pluripotent stem cells(hPSCs)have been suggested as a potential source for the production of blood cells for clinical *** two decades,almost all types of blood cells can be successfully generated from hPSCs through various differentiated ***,with a deeper understanding of hematopoiesis,higher efficiency of generating progenitors and precursors of blood cells from hPSCs is ***,how to generate large-scale mature functional cells from hPSCs for clinical use is still *** this review,we summarized recent approaches that generated both hematopoietic stem cells and mature lineage cells from hPSCs,and remarked their efficiency and mechanisms in producing mature functional *** also discussed the major challenges in hPSC-derived products of blood cells and provided some potential *** review summarized efficient,simple,and defined methodologies for developing good manufacturing practice standards for hPSC-derived blood cells,which will facilitate the translation of these products into the clinic.

关键词： Human pluripotent stem cells Hematopoietic differentiation Hematopoietic stem cells Blood cells

Efficient expansion of rare human circulating hematopoietic stem/progenitor cells in steady-state blood using a polypeptide-forming 3D culture

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Protein & Cell 2022年第11期13卷 808-824页

作者： Yulin Xu Xiangjun Zeng Mingming Zhang Binsheng Wang Xin Guo Wei Shan Shuyang Cai qian Luo Honghu Li Xia Li Xue Li Hao Zhang Limengmeng Wang Yu Lin Lizhen Liu Yanwei Li Meng Zhang Xiaohong Yu pengxu qian He Huang Bone Marrow Transplantation Center First Affiliated HospitalZhejiang University School of MedicineHangzhou 310012China Liangzhu Laboratory Zhejiang University Medical CenterHangzhou 311121China Institute of Hematology Zhejiang UniversityHangzhou 310012China Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy Hangzhou 310012China Core Facilities Zhejiang University School of MedicineHangzhou 310012China Dr.Li Dak Sum&Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang UniversityHangzhou 310012China

Although widely applied in treating hematopoietic malignancies,transplantation of hematopoietic stem/progenitor cells(HSPCs)is impeded by HSPC *** circulating HSPCs(cHSPCs)in steady-state blood could be used as an alternative source remains largely *** we develop a three-dimensional culture system(3DCS)including arginine,glycine,aspartate,and a series of ***-day culture of peripheral blood mononuclear cells(PBMNCs)in 3DCS led to 125-and 70-fold increase of the frequency and number of CD34+***,3DCS-expanded cHSPCs exhibited the similar reconstitution rate com-pared to CD34+HSPCs in bone ***,3DCS fabricated an immunomodulatory niche,secreting cytokines as TNF to support cHSPC survival and ***,3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC *** 3DCS successfully expands rare cHSPCs,providing an alternative source for the HSPC therapy,particularly for the patients/donors who have failed in HSPC mobilization.

关键词： hematopoietic stem/progenitor cell transplantation peripheral blood mononuclear cells expansion mobilization three-dimensional culture selfrenewal and multilineage differentiation

Epigenetic regulation of hematopoietic stem cell homeostasis

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Blood Science 2019年第1期1卷 19-28页

作者： Penglei Jiang Hui Wang Jiachen Zheng Yingli Han He Huang pengxu qian Center of Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated HospitalZhejiang University School of MedicineHangzhouP.R.China Institute of Hematology Zhejiang Engineering Laboratory for Stem Cell and ImmunotherapyZhejiang UniversityHangzhouP.R.China

As one of the best characterized adult stem cells,hematopoietic stem cell(HSC)homeostasis is of great importance to hematopoiesis and immunity due to HSC’s abilities of self-renewal and multi-lineage differentiation into functional blood ***,excessive self-renewal of HSCs can lead to severe hematopoietic malignancies like leukemia,whereas deficient selfrenewal of HSCs may result in HSC exhaustion and eventually apoptosis of specialized cells,giving rise to abnormalities such as immunodeficiency or *** HSC homeostasis is maintained has been studied for decades and regulatory factors can be generally categorized into two classes:genetic factors and epigenetic *** genetic factors such as signaling pathways or transcription factors have been well explored,recent studies have emerged the indispensable roles of epigenetic *** this review,we have summarized regulatory mechanisms of HSC homeostasis by epigenetic factors,including DNA methylation,histone modification,chromatin remodeling,non-coding RNAs,and RNA modification,which will facilitate applications such as HSC ex vivo expansion and exploration of novel therapeutic approaches for many hematological diseases.

关键词： Epigenetics Hematopoietic stem cells Homeostasis

Correction:Generating hematopoietic cells from human pluripotent stem cells:approaches,progress and challenges

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Cell Regeneration 2023年第1期12卷 67-69页

Correction:Cell Regen 12,31(2023).https://***/10.1186/s13619-023-00175-6 Following publication of the original article(Zheng et al.2023),the authors reported that Figs.1 and 2 were in the wrong *** correct Figs.1 and ... 详细信息

关键词： wrong challenges corrected

Correction:Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

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Signal Transduction and Targeted Therapy 2021年第12期6卷 3798-3798页

作者： Xia Li Mi Shao Xiangjun Zeng pengxu qian He Huang Bone Marrow Transplantation Center The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou People’s Republic of China Liangzhu Laboratory Zhejiang University Medical Center 1369 West Wenyi Road Hangzhou 311121 People’s Republic of China Institute of Hematology Zhejiang University Hangzhou Zhejiang People’s Republic of China Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy Hangzhou Zhejiang People’s Republic of China Center of Stem Cell and Regenerative Medicine Zhejiang University School of Medicine Hangzhou People’s Republic of China

Since the publication of this review1,the authors noticed one inadvertent mistake occurred in Fig.6c that needs to be *** correct Fig.6 is provided as *** detail,"Human-derived CAR-T cells"has been replaced by"Mouse-derived CAR-T cells"in the revised *** key findings of the article are not affected by these *** original review article has been corrected.

关键词： diseases cytokine release