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Heat shock protein 20 promotes sirtuin 1-dependent cell proliferation in induced pluripotent stem cells

World Journal of Stem Cells 2021年第6期13卷 659-669页

作者： Mujib Ullah Nicole Pek Min Qian gustavo yannarelli Asma Akbar Institute for Immunity and Transplantation Stem Cell Biology and Regenerative MedicineSchool of MedicineStanford UniversityStanfordCA 94304United States Immunology and School of Medicine Stanford UniversityStanfordCA 94304United States Laboratorio de Regulación Génica y Células Madre Instituto de Medicina TraslacionalTrasplante y Bioingeniería(IMeTTyB)Universidad Favaloro-CONICETBuenos Aires 1078Argentina Institute for Molecular Medicine School of MedicineStanford UniversityStanfordCA 94304United States

BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that protect cells against cellular stresses or ***,it has been increasingly recognized that they also play crucial roles in regulating fundamental cellular ***20 has been implicated in cell proliferation,but conflicting studies have shown that it can either promote or suppress *** underlying mechanisms by which HSP20 regulates cell proliferation and pluripotency remain *** the effect of HSP20 on cell proliferation has been recognized,its role in inducing pluripotency in human-induced pluripotent stem cells(iPSCs)has not been *** To evaluate the efficacy of HSP20 overexpression in human iPSCs and evaluate the ability to promote cell *** purpose of this study was to investigate whether overexpression of HSP20 in iPSCs can increase pluripotency and *** We used iPSCs,which retain their potential for cell ***20 overexpression effectively enhanced cell proliferation and *** of HSP20 in iPSCs was characterized by immunocytochemistry staining and realtime polymerase chain *** also used cell culture,cell counting,western blotting,and flow cytometry analyses to validate HSP20 overexpression and its *** This study demonstrated that overexpression of HSP20 can increase the pluripotency in ***,by overexpressing HSP20 in iPSCs,we showed that HSP20 upregulated proliferation markers,induced pluripotent genes,and drove cell proliferation in a sirtuin 1(SIRT1)-dependent *** data have practical applications in the field of stem cell-based therapies where the mass expansion of cells is needed to generate large quantities of stem cell-derived cells for transplantation *** We found that the overexpression of HSP20 enhanced the proliferation of iPSCs in a SIRT1-dependent ***,we established the distinct crosstalk between HSP20 and SIR

关键词： Heat shock proteins Stem cells Proliferation Induced pluripotent stem cells Sirtuin-1 Heat shock protein 20 Pluripotency

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Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients

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Oncology Research 2023年第3期31卷 361-374页

作者： FRANCISCO RAÚL BORZONE MARÍA BELÉN GIORELLO LEANDRO MARCELO MARTINEZ MARÍA CECILIA SANMARTIN LEONARDO FELDMAN FEDERICO DIMASE EMILIO BATAGELJ gustavo yannarelli NORMA ALEJANDRA CHASSEING Laboratorio de Inmunohematología Instituto de Biología y Medicina Experimental(IBYME)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Buenos AiresArgentina Division of Hematology and Medical Oncology Department of MedicineWeill Cornell Medical CollegeNew YorkUSA Laboratorio de Regulación Génica y Células Madre Instituto de Medicina TraslacionalTrasplante y Bioingeniería(IMeTTyB)Universidad Favaloro-CONICETBuenos AiresArgentina Facultad de Ciencias de la Salud Universidad Nacional del Centro de la Provincia de Buenos Aires(UNCPB)TandilBuenos AiresArgentina Servicio de Hematología Hospital Militar CentralBuenos AiresArgentina Servicio de Oncología Hospital Militar CentralBuenos AiresArgentina

Breast cancer is the predominant form of carcinoma among women worldwide,with 70%of advanced patients developing bone metastases,with a high mortality *** this sense,the bone marrow(BM)mesenchymal stem/stromal cells(MSCs)are critical for BM/bone homeostasis,and failures in their functionality,transform the BM into a premetastatic niche(PMN).We previously found that BM-MSCs from advanced breast cancer patients(BCPs,infiltrative ductal carcinoma,stage III-B)have an abnormal *** work aims to study some of the metabolic and molecular mechanisms underlying MSCs shift from a normal to an abnormal profile in this group of patients.A comparative analysis was undertaken,which included self-renewal capacity,morphology,proliferation capacity,cell cycle,reactive oxygen species(ROS)levels,and senescence-associatedβ‑galactosidase(SA‑β‑gal)staining of BMderived MSCs isolated from 14 BCPs and 9 healthy volunteers(HVs).Additionally,the expression and activity of the telomerase subunit TERT,as well as telomere length,were *** levels of pluripotency,osteogenic,and osteoclastogenic genes(OCT-4,SOX-2,M-CAM,RUNX-2,BMP-2,CCL-2,M-CSF,and IL-6)were also *** results showed that MSCs from BCPs had reduced,self-renewal and proliferation *** cells also exhibited inhibited cell cycle progression and phenotypic changes,such as an enlarged and flattened ***,there was an increase in ROS and senescence levels and a decrease in the functional capacity of TERT to preserve telomere *** also found an increase in pro-inflammatory/pro-osteoclastogenic gene expression and a decrease in pluripotency gene *** conclude that these changes could be responsible for the abnormal functional profile that MSCs show in this group of patients.

关键词： Mesenchymal stem/stromal cells Senescence Breast cancer Bone marrow Pre-metastatic niche Bone metastasis

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Applications of artificial intelligence in, early detection of cancer, clinical diagnosis and personalized medicine

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Artificial Intelligence in Cancer 2020年第2期1卷 39-44页

作者： Mujib Ullah Asma Akbar gustavo yannarelli Institute for Immunity TransplantationStem Cell Biology and Regenerative MedicineSchool of MedicineStanford UniversityPalo AltoCA 94304United States Molecular Medicine Department of RadiologySchool of MedicineStanford UniversityPalo AltoCA 94304United States Laboratorio de Regulación Génica y Células Madre Instituto de Medicina TraslacionalTrasplante y BioingenieríaUniversidad Favaloro-CONICETBuenos Aires 1078Argentina

Artificial intelligence(AI)refers to the simulation of human intelligence in machines programmed to convert raw input data into decision-making actions,like *** programs are designed to make decisions,often using deep learning and computer-guided programs that analyze and process raw data into clinical decision making for effective *** techniques for predicting cancer at an early stage are needed as conventional methods have poor accuracy and are not applicable to personalized *** has the potential to use smart,intelligent computer systems for image interpretation and early diagnosis of *** has been changing almost all the areas of the medical field by integrating with new emerging *** has revolutionized the entire health care system through innovative digital diagnostics with greater precision and *** is capable of detecting cancer at an early stage with accurate diagnosis and improved survival *** is an innovative technology of the future that can be used for early prediction,diagnosis and treatment of cancer.

关键词： Artificial intelligence Cancer Clinical tumor prediction Early detection of cancer Clinical diagnosis Personalized medicine

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