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CAPE promotes the expansion of human umbilical cord blood-derived hematopoietic stem and progenitor cells in vitro

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Science China(Life Sciences) 2014年第2期57卷 188-194页

作者： LIU YiMing ZHANG BoWen ZHANG Jing WANG SiHan YAO HaiLei HE LiJuan CHEN Lin YUE Wen LI YanHua PEI XueTao Stem cell and regenerative medicine Lab Beijing Institute of Transfusion Medicine

Due to the low number of collectable stem cells from single umbilical cord blood(UCB)unit,their initial uses were limited to pediatric *** applications of UCB hematopoietic stem and progenitor cells(HSPCs)would become feasible if there were a culture method that can effectively expand HSPCs while maintaining their self-renewal *** recent years,numerous attempts have been made to expand human UCB HSPCs in *** this study,we report that caffeic acid phenethyl ester(CAPE),a small molecule from honeybee extract,can promote in vitro expansion of *** with CAPE increased the percentage of HSPCs in cultured mononuclear ***,culture of CD34+HSPCs with CAPE resulted in a significant increase in total colony-forming units and high proliferative potential colony-forming ***-forming unit-erythroid was the mostly affected colony type,which increased more than 3.7-fold in 1μg mL 1CAPE treatment group when compared to the *** appears to induce HSPC expansion by upregulating the expression of SCF and HIF1-α.Our data suggest that CAPE may become a potent medium supplement for in vitro HSPC expansion.

关键词： hematopoietic stem and progenitor cells caffeic acid phenethyl ester expansion

Umbilical cord:an unlimited source of cells differentiable towards dopaminergic neurons

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Neural Regeneration research 2017年第7期12卷 1186-1192页

作者： Mahdi Eskandarian Boroujeni Mossa Gardaneh Department of Stem cells and regenerative medicine Faculty of Medical Biotechnology National Institute of Genetic Engineering and Biotechnology Tehran Iran

cell replacement therapy utilizing mesenchymal stem cells as its main resource holds great promise for ultimate treatment of human neurological ***＇s disease（PD）is a common,chronic neurodegenerative disorder hallmarked by localized degeneration of a specific set of dopaminergic neurons within a midbrain *** specific cell type and confined location of degenerating neurons make cell replacement therapy ideal for PD treatment since it mainly requires replenishment of lost dopaminergic neurons with fresh and functional *** as well as exogenous cell sources have been identified as candidate targets for cell replacement therapy in *** this review,umbilical cord mesenchymal stem cells（UCMSCs）are discussed as they provide an inexpensive unlimited reservoir differentiable towards functional dopaminergic neurons that potentially lead to long-lasting behavioral recovery in PD *** also present mi RNAs-mediated neuronal differentiation of *** UCMSCs bear a number of outstanding characteristics including their non-tumorigenic,low-immunogenic properties that make them ideal for cell replacement therapy ***,more investigations as well as controlled clinical trials are required to thoroughly confirm the efficacy of UCMSCs for therapeutic medical-grade applications in PD.

关键词： nerve regeneration umbilical cord mesenchymal stem cells differentiation neuronal dopaminergicneurons dopamine substantia nigra ventral mesencephalon Parkinson's disease cell replacement therapy neural regeneration

Metabolism of pluripotent stem cells

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Frontiers in Biology 2016年第5期11卷 355-365页

作者： Liang Hu Edward Trope Qi-Long Ying Eli and Edythe Broad Center for regenerative medicine and Stem cell research at USC Department of Stem Cell Biology and Regenerative Medicine Keck School of Medicine University of Southern California Los Angeles CA 90033 USA

BACKGROUND： Recently, growing attention has been directed toward stem cell metabolism, with the key observation that metabolism not only fuels the proper functioning of stem cells but also regulates the fate of these cells. There seems to be a clear link between the self-renewal ofpluripotent stem cells （PSCs）, in which cells proliferate indefinitely without differentiation, and the activity of specific metabolic pathways. The unique metabolism in PSCs plays an important role in maintaining pluripotency by regulating signaling pathways and resetting the epigenome. OBJECTIVE： To review the most recent publications concerning the metabolism of pluripotent stem cells and the role of metabolism in PSC self-renewal and differentiation. METHODS： A systematic literature search related to the metabolism of PSCs was conducted in databases including Medline, Embase, and Web of Science. The search was performed without language restrictions on all papers published before May 2016. The following keywords were used：＂metabolism＂ combined with either ＂embryonic stem cell＂ or ＂epiblast stem cell.＂ RESULTS： Hundreds of papers focusing specifically on the metabolism of pluripotent stem cells were uncovered and summarized. CONCLUSION： Identifying the specific metabolic pathways involved in pluripotency maintenance is crucial for progress in the field of developmental biology and regenerative medicine. Additionally, better understanding of the metabolism in PSCs will facilitate the derivation and maintenance of authentic PSCs from species other than mouse, rat, and human.

关键词： metabolism pluripotent stem cells pluripotency epigenetics

Cancer cell cycle heterogeneity as a critical determinant of therapeutic resistance

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Genes & Diseases 2024年第1期11卷 189-204页

作者： Ebrahim H.Maleki Ahmad Reza Bahrami Maryam M.Matin Department of Biology Faculty of ScienceFerdowsi University of Mashhad*** MashhadIran Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian University31-007 KrakowPoland Doctoral School of Exact and Natural Sciences Jagiellonian University30-348 KrakowPoland Industrial biotechnology research group Institute of BiotechnologyFerdowsi University of Mashhad*** MashhadIran Novel Diagnostics and Therapeutics research group Institute of BiotechnologyFerdowsi University of Mashhad***MashhadIran Stem cell and regenerative medicine research group Iranian Academic Center for EducationCulture and Research(ACECR)Khorasan Razavi Branch917751376 MashhadIran

Intra-tumor heterogeneity is now arguably one of the most-studied topics in tumor biology,as it represents a major obstacle to effective cancer *** tumor cells are highly diverse at genetic,epigenetic,and phenotypic levels,intra-tumor heterogeneity can be assumed as an important contributing factor to the nullification of chemotherapeutic effects,and recurrence of the *** on the role of heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics and behavior during cancer progression and treatment;herein,we aim to establish a comprehensive definition for adaptation of neoplastic cells against *** discuss two parallel and yet distinct subpopulations of tumor cells that play pivotal roles in reducing the effects of chemotherapy:"resistant"and"tolerant"***,this review also highlights the impact of the quiescent phase of the cell cycle as a survival mechanism for cancer *** understanding the mechanisms under-lying the quiescence,it provides an insightful perspective on cancer stem cells(CsCs)and their dual and intertwined functions based on their cell cycle state in response to ***-over,CSCs,epithelial-mesenchymal transformed cells,circulating tumor cells(CTCs),and disseminated tumor cells(DTCs),which are mostly in a quiescent state of the cell cycle are proved to have multiple biological links and can be implicated in our viewpoint of cell cycle heterogeneity in ***,increasing our knowledge of cell cycle heterogeneity is a key to identifying new therapeutic solutions,and this emerging concept may provide us with new opportunities to prevent the dreadful cancer recurrence.

关键词： Cancer stem cells(CSCs) Carcinoma cell cycle heterogeneity Quiescence therapy resistance therapy tolerance Tumor dormancy

A tunable, rapid, and precise drug control of protein expression by combining transcriptional and post-translational regulation systems

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Journal of Genetics and Genomics 2020年第11期47卷 705-712页

作者： Li Li Hongyi Meng Jianmin Zhang Yang Liu Qingjian Zou Yi Gao Huaqiang Yang Liangxue Lai Department of Hepatobiliary Surgery II Guangdong Provincial Research Center for Artificial Organ and Tissue EngineeringInstitute of Regenerative MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou510282China CAS Key Laboratory of regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou510530China School of biotechnology and Health Sciences Wuyi UniversityJiangmen529020China College of Animal Science South China Agricultural UniversityGuangzhou510642China

Rapid,precise,and tunable regulation of protein abundance would be significantly useful in a variety of biotechnologies and biomedical ***,we describe a system that allows tunable and rapid drug control of gene expression for either gene activation or inactivation in mammalian *** construct the system by coupling Tet-on 3 G and small molecule-assisted shutoff systems,which can respectively induce transcriptional activation and protein degradation in the presence of corresponding small *** dual-input drug inducer regulation system facilitates a bidirectional control of gene *** gene of interest can be precisely controlled by dual small molecules in a broad dynamic range of expression from overexpression to complete silence,allowing gene function study in a comprehensive expression *** results reveal that the bidirectional control system enables sensitive dosage-and time-dependent regulation for either turn-on or shutoff of gene *** also apply this system for inducible genome editing and gene activation mediated by clustered regularly interspaced short palindromic *** system provides an integrated platform for studying multiple biological processes by manipulating gene expression in a more flexible way.

关键词： Protein abundance Tet-on 3G SMASh Gene expression CRISPR Small molecule

Effects of lysophosphatidic acid on human periodontal ligament stem cells from teeth extracted from dental patients

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The Journal of Biomedical research 2019年第2期33卷 122-130页

作者： Byung Cheol Kim Jae-In Song Kyoung-Ha So Sang-Hwan Hyun Laboratory of Veterinary Embryology and biotechnology Veterinary Medical Center and College of Veterinary MedicineChungbuk National University Institute of Stem cell & regenerative medicine Chungbuk National University

Despite their potential applications in future regenerative medicine, periodontal ligament stem cells(PDLSCs) are difficult to obtain in large amounts from patients. Therefore, maintaining sternness while expanding the cell numbers for medical use is the key to transitioning PDLSCs from the bench to the clinic. Lysophosphatidic acid(LPA), which is present in the human body and saliva, is a signaling molecule derived from phospholipids. In this study, we examined the effects of LPA on sternness maintenance in human PDLSCs. Several spindle-shaped and fibroblast-like periodontal ligament stem-like cell lines were established from PDLSC isolation. Among these cell lines, the most morphologically appropriate cell line was characterized. The expression levels of OCT4, NANOG(a stem cell marker), and CD90(a mesenchymal stem cell marker) were high. However, CD73(a negative marker of mesenchymal stem cells) expression was not observed. Notably, immunofluorescence analysis identified the expression of STRO-1, CD146(a mesenchymal stem cell marker), and sex determining region Y-box 2 at the protein level. In addition, lipid droplets were stained by Oil red O after the induction of adipogenesis for 21 days, and mineralized nodules were stained by Alizarin Red S after the induction of osteogenesis for 14 days. Alkaline phosphate staining also demonstrated the occurrence of osteogenesis. In summary, we established a human PDLSC line, which could be applied as a cell source for tissue regeneration in dental patients. However, further studies are needed to determine the detailed effects of LPA on PDLSCs.

关键词： periodontal ligament stem cell lysophosphatidic acid stemness primary cell culture

RNA binding protein 24 deletion disrupts global alternative splicing and causes dilated cardiomyopathy

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Protein & cell 2019年第6期10卷 405-416页

作者： Jing Liu Xu Kong Mengkai Zhang Xiao Yang Xiuqin Xu The Institute of Stem cell and regenerative medicine Medical College Xiamen University Xiamen 361100 China State Key Laboratory of Proteomics Genetic Laboratory of Development and Disease Institute of Biotechnology Beijing 100071 China

RNA splicing contributes to a broad spectrum of posttranscriptional gene regulation during normal development, as well as pathological manifestation of heart diseases. However, the functional role and regulation of splicing in heart failure remain poorly understood. RNA binding protein (RBP), a major component of the splicing machinery, is a critical factor in this process. RNA binding motif protein 24 (RBM24) is a tissue-specific RBP which is highly expressed in human and mouse heart. Previous studies demonstrated the functional role of RBM24 in the embryonic heart development. However, the role of RBM24 in postnatal heart development and heart disease has not been investigated. In this paper, using conditional RBM24 knockout mice, we demonstrated that ablation of RBM24 in postnatal heart led to rapidly progressive dilated cardiomyopathy (DCM), heart failure, and postnatal lethality. Global splicing profiling revealed that RBM24 regulated a network of genes related to cardiac function and diseases. Knockout of RBM24 resulted in misregulation of these splicing transitions which contributed to the subsequent development of cardiomyopathy. Notably, our analysis identified RBM24 as a splice factor that determined the splicing switch of a subset of genes in the sacomeric Z-disc complex, including Titin, the major disease gene of DCM and heart failure. Together, this study identifies regulation of RNA splicing by RBM24 as a potent player in remodeling of heart during postnatal development, and provides novel mechanistic insights to the pathogenesis of DCM.

关键词： RNA binding protein RBM24 dilated cardiomyopathy alternative splicing heart failure

Down-regulation of Halr1 during induced differentiation of embryonal carcinoma P19 cells

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BIOcell 2019年第3期43卷 145-154页

作者： ZAHRA HOSSEININIA SARA SOLTANIAN NASER MAHDAVI-SHAHRI HESAM DEHGHANI Division of biotechnology Faculty of Veterinary MedicineFerdowsi University of MashhadMashhadIran Department of Biology Faculty of SciencesShahid Bahonar University of KermanKermanIran Department of Biology Faculty of SciencesFerdowsi University of MashhadMashhadIran Stem cells and regenerative medicine research group Research Institute of BiotechnologyFerdowsi University of MashhadMashhadIran

Maintenance of pluripotency depends to diverse regulatory *** in embryonic stem cells(ESCs)have indicated that large intergenic non-coding RNAs(lincRNAs)are involved in the regulatory network of ***,the presence and function of pluripotency-associated lincRNAs in cancer cells with pluripotency features are *** this study,we used embryonal carcinoma(EC)P19 cell lines to investigate the expression level of Halr1 in pluripotency and retinoic acid(RA)-induced differentiated ***-regulation of pluripotency associated factors such as OCT4,NANOG,SSEA1 and alkaline phosphatase at transcript and protein levels were used to confirm the differentiated status of P19 *** measurement of Halr1 transcript levels revealed a 79% decrease during RA-induced differentiation of P19 *** results indicate that upon exiting the pluripotency state the expression level of Halr1 similar to core pluripotency factors is remarkably reduced.

关键词： Differentiation Halr1 lincRNA Pluripotency P19 cell Retinoic acid

Toll-like receptor 4 and protease-activated receptor 2 in physiology and pathophysiology of the nervous system:more than just receptor cooperation?

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Neural Regeneration research 2019年第7期14卷 1196-1201页

作者： Darius Widera Rocío Martínez Aguilar Graeme S.Cottrell Stem cell Biology and regenerative medicine group School of PharmacyUniversity of ReadingWhiteknights campus Unidad de Inmunología IBIMERUniversidad de Granada cellular and Molecular Neuroscience School of PharmacyUniversity of Reading

Toll-like receptor 4(TLR4) and protease-activated receptor 2(PAR2) play pivotal roles in the mammalian innate immune ***,in addition to their involvement in detection of invading pathogens,PAR2 and TLR4 modulate the levels of cell death-induced sterile inflammation by activating pro-or anti-inflammatory downstream signaling *** the central nervous system,there is emerging evidence that both receptors are involved in synaptic transmission and brain ***,due to their prominent role in mediating neuroinflammation,PAR2 and TLR4 are associated with development and progression of neurodegenerative disorders including but not limited to Alzheimer's disease,Parkinson's disease and multiple *** this article,we summarise the current knowledge on the cooperation between PAR2 and TLR4,discuss the potential cross-talk levels and highlight the impact of the cross-coupling on neuroinflammation.

关键词： signaling inflammation proteases myeloid of differentiation primary response gene 88 TIR-domain containing adaptor inducing interferon lipopolysaccharide TLR4 PAR2