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Genes & Diseases 2024年第3期11卷 26-29页

作者： Xiangyu Dong Yannian Gou Meichun Guo Jiamin Zhong Aohua Li Ailing Hao wei zeng.rex c.haydon Hue H.Luu Russell R.Reid Tongchuan He Yan Xu Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine And Department of Clinical BiochemistryCollege of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Laboratory of craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Institute of Sports Medicine Beijing Key Laboratory of Sports InjuriesPeking University Third HospitalBejing 100191China

With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport *** for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.

关键词： transport methods simplified

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao wei zeng connie chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff rex c.haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-catenin cancer canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo wei zeng connie chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff rex c.haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-chuan He Lewis L.Shi chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PcP,and the noncanonical Wnt/ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

Niclosamide(NA)overcomes cisplatin resistance in human ovarian cancer

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Genes & Diseases 2023年第4期10卷 1687-1701页

作者： Linjuan Huang Jing Zhang Youling Deng Hao Wang Piao Zhao Guozhi Zhao wei zeng Yonghui Wang connie chen William Wagstaff rex c.haydon Russell R.Reid Tong-chuan He Le Shen Hue H.Luu Ling Zhao Departments of Obstetrics and Gynecology Orthopaedic Surgery and UrologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400046China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Neurology The Second Affiliated Hospital of Jianghan UniversityWuhanHubei 430050China Department of clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Laboratory of craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Surgery The University of Chicago Medical CenterChicagoIL 60637USA

Ovarian cancer(Oc)is one of the most lethal malignancies of the female reproduc-tive *** patients are usually diagnosed at advanced stages due to the lack of early *** standard treatment for Oc includes a combination of debulking surgery and platinum-taxane chemotherapy,while several targeted therapies have recently been approved for maintenance *** vast majority of Oc patients relapse with chemoresistant tu-mors after an initial ***,there is an unmet clinical need to develop new therapeu-tic agents to overcome the chemoresistance of *** anti-parasite agent niclosamide(NA)has been repurposed as an anti-cancer agent and exerts potent anti-cancer activities in human cancers including ***,we investigated whether NA could be repurposed as a therapeutic agent to overcome cisplatin-resistant(cR)in human Oc *** this end,we first established two cR lines SKOV3cR and OVcAR8cR that exhibit the essential biological characteristics of cisplatin resistance in human *** showed that NA inhibited cell proliferation,sup-pressed cell migration,and induced cell apoptosis in both cR lines at a low micromole ***,NA inhibited multiple cancer-related pathways including AP1,ELK/SRF,HIF1,and TcF/LEF,in SKOV3cR and OVcAR8cR *** was further shown to effectively inhibit xenograft tumor growth of SKOV3cR ***,our findings strongly suggest that NA may be repurposed as an efficacious agent to combat cisplatin resistance in chemoresistant hu-man Oc,and further clinical trials are highly warranted.

关键词： chemotherapy resistance cisplatin Drug repurposing Niclosamide Ovarian cancer

Engineered nucleus-free mesenchymal stem cells (MScs) for the targeted delivery of therapeutics to disease site

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Genes & Diseases 2023年第2期10卷 310-312,I0001页

作者： Zander Schwartz Piao Zhao Annie Wang Guozhi Zhao wei zeng Yonghui Wang Hue H. Luu rex c. haydon Tong-chuan He Russell R. Reid Jason Strelzow School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Laboratory of craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Specialized therapeutic delivery, or use of pharmaceuticals and other biomaterials to target specific parts of the body or diseased tissue, has long been sought as an ideal way of treating human diseases. A recent article published in Nature Biomedical Engineering revealed an innovative strategy to engineer nucleus-free human mesenchymal stem cells (MScs) for targeted delivery of therapeutics to disease site.1 MScs have emerged as promising vehicles of therapeutic delivery.2,3 MScs are undifferentiated pluripotent stem cells derived from areas such as bone marrow and adipose tissue.4,5 MScs are sought after for their chemotaxis, or ability to home towards a chemical stimulus, and capacity for modification with elements such as chemoattractant receptors and adhesion molecules.1 These properties allow for site-specific and minimally-invasive therapeutic administration and treatment.

关键词： targeted delivery sought

Bone Morphogenic Protein 9(BMP9)/Growth Differentiation Factor 2(GDF2)modulates mouse adult hippocampal neurogenesis by regulating the survival of early neural progenitors

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Genes & Diseases 2023年第4期10卷 1175-1179页

作者： Mary Rose Rogers wei zeng Xian Zhang Ruidong Li Qiang wei Yuhan Kong Piao Zhao Guozhi Zhao Yonghui Wang Jiamin Zhong Yi Zhu rex c.haydon Hue H.Luu Russell R.Reid Daniel A.Peterson Michael J.Lee Tong-chuan He Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Graduate Program committee on Genetics Genomics and System BiologyThe University of ChicagoChicagoIL 60637USA Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Neurology The Second Affiliated Hospital of Jianghan UniversityWuhanHubei 430000China Department of Orthopaedic Surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Department of clinical Laboratory Medicine Rehabilitation MedicineOrthopaedic Surgery and UrologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Endocrinology Shanghai Jiao-Tong University School of MedicineShanghai 200000China Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopaedic Surgery Beijing HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA center for Stem cell and Regenerative Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA

Adult neurogenesis occurs in two specialized regions of the mammalian brain,the subventricular zone(SVZ)and the subgranular zone(SGZ)of the dentate gyrus(DG).^(1)Adult hippocampal neural stem cells(NScs),referred to as Type 1 cells represented by radial glia-like cells(RGLs),generate Type 2 cells that are divided into Type 2a and Type 2 b subpopulations,the latter of which give rise to Type 3 cells(neuroblasts).

关键词： neural progenitor ventricular

SV40 large T antigen-induced immortalization reprograms mouse cardiomyocyte progenitors with mesenchymal stem cell characteristics and osteogenic potential

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Genes & Diseases 2023年第4期10卷 1161-1164页

作者： Yichun Yu Jiamin Zhong connie chen Yannian Gou Guozhi Zhao Piao Zhao Yonghui Wang wei zeng Annie Wang William D.Wagstaff Jr rex c.haydon Tong-chuan He Russell R.Reid Michael J.Lee Hue H.Luu Jiaming Fan Emergency Department Beijing Hospitaland The National Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100051China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Diagnostic MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200025China Department of Neurology The Second Affiliated Hospital of Jianghan UniversityWuhanHubei 430050China Laboratory of craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

While progenitor cell-based cardiomyocyte regeneration holds great promise of repairing an injured heart,primary cardiomyogenic progenitors(cPs)have a limited life span in culture,hampering the use of cPs for in vitro and in vivo *** previously isolated primary cPs from mouse E15.5 fetal heart,and reversibly immortalized them with SV40 large T antigen(SV40 LTA),resulting in immortalized cPs(icPs),which maintain long-term proliferation and ex-press cardiomyogenic markers and retain differentiation potential under appropriate differentiation conditions.

关键词： progenitor cardio potential

Breast cancer development and progression:Risk factors,cancer stem cells,signaling pathways,genomics,and molecular pathogenesis

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Genes & Diseases 2018年第3期5卷 77-106页

作者： Yixiao Feng Mia Spezia Shifeng Huang chengfu Yuan Zongyue zeng Linghuan Zhang Xiaojuan Ji wei Liu Bo Huang Wenping Luo Bo Liu Yan Lei Scott Du Akhila Vuppalapati Hue H.Luu rex c.haydon Tong-chuan He Guosheng Ren chongqing Key Laboratory of Molecular Oncology and Epigenetics Departments of General SurgeryClinical Laboratory MedicineOrthopaedic SurgeryPlastic Surgery and Burnand OtolaryngologyHead and Neck SurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichang 443002China Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine Chongqing Medical UniversityChongqing 400016China Stem cell Biology and Therapy Laboratory Ministry of Education Key Laboratory of Child Development and DisordersThe Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang 330006China chongqing Key Laboratory for Oral Diseases and Biomedical Sciences The Affiliated Hospital of StomatologyChongqing Medical UniversityChongqing 401147China Student Inquiry Research Program Illinois Mathematics and Science Academy(IMSA)AuroraIL 60506USA

As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global *** cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the *** the risk factors associated with this cancer varies with respect to other cancers,genetic predisposition,most notably mutations in BRcA1 or BRcA2 gene,is an important causative factor for this *** cancers can begin in different areas of the breast,such as the ducts,the lobules,or the tissue in *** the large group of diverse breast carcinomas,there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor *** is important to distinguish between the various subtypes because they have different prognoses and treatment *** there are remarkable parallels between normal development and breast cancer progression at the molecular level,it has been postulated that breast cancer may be derived from mammary cancer stem *** breast development and mammary stem cells are regulated by several signaling pathways,such as estrogen receptors(ERs),HER2,and Wnt/b-catenin signaling pathways,which control stem cell proliferation,cell death,cell differentiation,and cell ***,emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer,especially for triple-negative breast *** review provides a comprehensive survey of the molecular,cellular and genetic aspects of breast cancer.

关键词： BRcA1/2 Breast cancer cancer stem cells Estrogen receptors HER2 Noncoding RNAs Triple-negative breast cancer Tumor heterogeneity

Establishment and functional characterization of the reversibly immortalized mouse glomerular podocytes(imPODs)

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Genes & Diseases 2018年第2期5卷 137-149页

作者： Xinyi Yu Liqun chen Ke Wu Shujuan Yan Ruyi Zhang chen Zhao Zongyue zeng Yi Shu Shifeng Huang Jiayan Lei Xiaojuan Ji chengfu Yuan Linghuan Zhang Yixiao Feng wei Liu Bo Huang Bo Zhang Wenping Luo Xi Wang Bo Liu rex c.haydon Hue H.Luu Tong-chuan He Hua Gan Departments of Nephrology Orthopaedic SurgeryCardiologyGeneral SurgeryPlastic Surgeryand Clinical Laboratory MedicineThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine and the Affiliated Hospitals of Chongqing Medical UniversityChongqing400016China Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichang443002China Department of clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang330031China Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery The Second Hospital of Lanzhou UniversityLanzhou730030China

Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of *** the viability and structural integrity of podocytes is critical to the clinical management of glomerular diseases,which requires a thorough understanding of podocyte cell *** mature podocytes lose proliferative capacity,a conditionally SV40 mutant tsA58-immortalized mouse podocyte line(designated as tsPc)was established from the Immortomouse over 20 years ***,the utility of the tsPc cells is hampered by the practical inconvenience of culturing these *** this study,we establish a user-friendly and reversibly-immortalized mouse podocyte line(designated as imPOD),on the basis of the tsPc cells by stably expressing the wildtype SV40 T-antigen,which is flanked with FRT *** show the imPOD cells exhibit long-term high proliferative activity,which can be effectively reversed by FLP *** imPOD cells express most podocyte-related markers,including WT-1,Nephrin,Tubulin and Vinculin,but not differentiation marker *** imPOD cells do not form tumor-like masses in *** further demonstrate that TGFb1 induces a podocyte injury-like response in the FLP-reverted imPOD cells by suppressing the expression of slit diaphragm-associated proteins P-cadherin and ZO-1 and upregulating the expression of mesenchymal markers,a-SMA,Vimentin and Nestin,as well as fibrogenic factors cTGF and ***,our results strongly demonstrate that the newly engineered im-POD cells should be a valuable tool to study podocyte biology both under normal and under pathological conditions.

关键词： chronic kidney disease FLP recombinase Glomerular disease Glomerulus Immortalization Nephropathy Podocyte SV40 T antigen

Molecular pathogenesis and therapeutic strategies of human osteosarcoma

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The Journal of Biomedical Research 2016年第1期30卷 5-18页

作者： Sahitya K Denduluri Zhongliang Wang Zhengjian Yan Jing Wang Qiang wei Maryam K Mohammed rex c.haydon Hue H Luu Tong-chuan He The University of chicago Pritzker School of Medicine and Molecular Oncology LaboratoryDepartment of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical UniversityChongqing 400016China

Osteosarcoma（OS）is a devastating illness with rapid rates of dissemination and a poor overall prognosis,despite aggressive standard-of-care surgical techniques and combination chemotherapy *** the molecular mechanisms involved in disease pathogenesis and progression may offer insight into new therapeutic *** in mesenchymal stem cell differentiation,abnormal expression of oncogenes and tumor suppressors,and dysregulation within various important signaling pathways have all been implicated in development of various disease *** such,a variety of basic science and translational studies have shown promise in identifying novel markers and modulators of these disease-specific *** out of these and similar investigations,a variety of emerging therapies are now undergoing various phases of OS clinical *** broadly include angiogenesis inhibitors,drugs that act on the bone microenvironment,receptor tyrosine kinase inhibitors,immune system modulators,and other radio-or chemo-sensitizing *** new forms of drug delivery are being developed simultaneously,the possibility of targeting tumors locally while minimizing systemic toxicityis is seemingly more achievable now than *** this review,we not only summarize our current understanding of OS disease processes,but also shed light on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.

关键词： osteosarcoma soft tissue tumors bone tumors cancer therapy osteogenic tumors osteogenic differentiation