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Reprogramming mature terminally differentiated adipocytes to induced pluripotent stem cells

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Science Bulletin 2015年第20期60卷 1752-1758页

作者： Tao Nie Wei Deng Xuefei Gao Wei Sun Xiaoyan Hui Hong Song Dajiang Qin Aimin Xu Peng Li Pentao Liu Liangxue Lai Donghai Wu Key Laboratory of regenerative biology Guangzhou Institute of Biomedicine and Health Chinese Academy of SciencesGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine School of Life Sciences Anhui University department of Pharmacology and Medicine The University of Hong Kong Wellcome Trust Institute

Mature adipocytes are terminally differentiated somatic cells. Here, we report the successful generation of induced pluripotent stem （iPS） cells from mouse mature adipocytes by forced expression of six transcription factors （Oct4, Sox2, c-Myc, Klf4, Rarγ, and Lrh1） with a piggyBac transposon-based strategy. The resulting iPS cells were pluripotent as evidenced by the fact that they stained positive for alkaline phosphatase, expressed high levels of key pluripotency markers including Oct4, Nanog, and SSEA1, and remained pluripotent on a 2i media. In vitro differen- tiation of the iPS cells showed that the cell derivatives of all three germ layers could be readily obtained through forma- tion of embryoid bodies. Most importantly, these adipocyte- derived iPS cells were capable of producing chimera with high frequencies when reintroduced into early-stage em- bryos and transmitted through the germ line. This study demonstrates that the new six-factor reprogramming tech- nology facilitates the reset of the terminally differentiated adipocytes to the ground state of pluripotency, enabling us to fully explore the potential of mature adipocytes as a viable cell source for regenerative medicine.

关键词： Adipocyte Induced pluripotent stem cell PiggyBac

Neural progenitor cells from human induced pluripotent stem cells generated less autogenous immune response

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Science China(Life Sciences) 2014年第2期57卷 162-170页

作者： HUANG Ke LIU PengFei LI Xiang CHEN ShuBin WANG LiHui QIN Li SU ZhengHui HUANG WenHao LIU JuLi JIA Bei LIU Jie CAI JingLei PEI DuanQing PAN GuangJin Key Laboratory of regenerative biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine Guangzhou Institutes of Biomedicine and HealthChinese Academy of Sciences department of Regeneration Medicine School of Pharmaceutical Science Jilin University Laboratory of Pathogen biology State Key Laboratory of Respiratory Disease department of Obstetrics and Gynecology Nanfang Hospital Southern Medical University

The breakthrough development of induced pluripotent stem cells(iPSCs)raises the prospect of patient-specific treatment for many diseases through the replacement of affected ***,whether iPSC-derived functional cell lineages generate a deleterious immune response upon auto-transplantation remains *** this study,we differentiated five human iPSC lines from skin fibroblasts and urine cells into neural progenitor cells(NPCs)and analyzed their *** co-culture with autogenous peripheral blood mononuclear cells(PBMCs),we showed that both somatic cells and iPSC-derived NPCs do not stimulate significant autogenous PBMC ***,a significant immune reaction was detected when these cells were co-cultured with allogenous ***,no significant expression of perforin or granzyme B was detected following stimulation of autogenous immune effector cells(CD3+CD8 T cells,CD3+CD8+T cells or CD3 CD56+NK cells)by NPCs in both PBMC and T cell co-culture *** results suggest that human iPSC-derived NPCs may not initiate an immune response in autogenous transplants,and thus set a base for further preclinical evaluation of human iPSCs.

关键词： induced pluripotent stem cells immunogenicity iPSC-derived neural progenitor cells

Serological Targeted Analysis of an ITIH4 Peptide Isoform: A Preterm Birth Biomarker and Its Associated SNP Implications

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Journal of Genetics and Genomics 2015年第9期42卷 507-510页

作者： Zhou Tan Zhongkai Hu Emily Y.Cai Cantas Alev Ting Yang Zhen Li Joyce Sung Yasser Yehia El-Sayed Gary M.Shaw David K.Stevenson Atul J.Butte Guojun Sheng Karl G.Sylvester Harvey J.Cohen Xuefeng B.Ling Institute of Developmental and regenerative biology Hangzhou Normal University department of Surgery Stanford University Lab for Early Embryogenesis RIKEN Center for Developmental Biology department of Obstetrics and Gynecology Stanford University department of Pediatrics Stanford University Stanford

Over 11% of all pregnancies in the US result in preterm birth, greatly contributing to perinatal morbidity and mortality （Goldenberg and Rouse, 1998）. Preterm birth etiologies remain largely unknown, and effective prevention methods have yet to be developed. The use of biofluid （e.g., serum or urine） for the analysis of the naturally occurring peptidome （MW 〈 4000） as a source of biomarkers has been reported for different diseases （Villanueva et al., 2006; Ling et al., 2010a, 2010b, 2010c, 2011）. Mass spectrometry-based profiling of naturally occurring peptides can provide an extensive in- ventory of serum peptides derived from either high-abundant endogenous circulating proteins or cell and tissue proteins （Liotta and Petricoin, 2006）.

关键词： Serological Targeted Analysis of an ITIH4 Peptide Isoform A Preterm Birth Biomarker and Its Associated SNP Implications SNP

RISC assembly and post-transcriptional gene regulation in Hepatocellular Carcinoma

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Genes & Diseases 2020年第2期7卷 199-204页

作者： Prasanna K.Santhekadur Divya P.Kumar department of Biochemistry Center of Excellence in Molecular Biology&Regenerative MedicineJSS Medical CollegeJSS Academy of Higher Education and ResearchMysoreIndia

RNA-induced silencing complex(RISC)is one of the basic eukaryotic cellular machinery which plays a pivotal role in post-transcriptional gene *** of miRNAs and their role in gene regulation have changed the course of modern *** method of gene silencing using small interfering RNAs and miRNAs has become major tool in molecular biology and genetic *** Carcinoma(HCC)is a very common malignancy of liver in developing countries and due to various risk factors;the prevalence of this disease is rapidly increasing throughout the *** exists an imbalance in interplay between oncogenes and tumor suppressor genes and their regulation plays a major role in HCC growth,development and *** regulatory function of RISC and miRNAs make them a very important mediators of cancer signaling in ***,targeting the RISC complex for HCC therapy is the need of the time.

关键词： Inflammation miRNA Oncogenes Regulation Tumor suppressor genes

Mutations of nuclear localization signals in mNANOG generate dominant negative mutants

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Chinese Science Bulletin 2009年第8期54卷 1361-1368页

作者： ZHANG Juan ZHANG XiaoFei PEI DuanQing Laboratory of Stem Cell biology Department of Biological Sciences & Biotechnology State Key Laboratory of Biomembrane and Membrane Biotechnology Institutes of Biomedicine School of Medicine Tsinghua University Beijing 100084 China Stem Cell and Cancer biology Group Key Laboratory of Regenerative Biology South China Institute for Stern Cell Biology and Regenerative Medicine Guangzhou Institute of Biomedicine and Health Chinese Academy of Sciences Guangzhou 510663 China

Mouse NANOG plays a critical role in maintaining self-renewal and pluripotency of embryonic stem ***,the precise mechanism of how mNANOG functions is still less ***,we report that mouse NANOG has two nuclear localization signals(NLS,RKQKMR and RMKCKR) which are responsible for the nuclear localization and transcriptional activity in the conserved homeobox *** mutants of mouse NANOG generate 3 mutants that are localized throughout the cells and lose the transactivation *** further prove that all three NLS mutants may interact with the wild-type mouse NANOG like NANOG dimerization itself and inhibit the wild-type mouse NANOG activity,acting as dominant negative *** NLS mutants of mouse NANOG may also inhibit activity of oct4 promoter in pluripotent cells,indicating that the NLS mutants can affect the endogenous mouse NANOG function in *** data suggest that the NLS mutants of mouse NANOG may be used as a tool to regulate NANOG activity in pluripotent cells.

关键词：核定位信号突变体显性 Nanog 突变小鼠胚胎干细胞转录活性职能作用

The role of L-arginine metabolism in neurocritical care patients

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Neural Regeneration Research 2022年第7期17卷 1446-1453页

作者： Marius Marc-Daniel Mader Patrick Czorlich department of Neurosurgery University Medical Center Hamburg-EppendorfHamburgGermany Institute for Stem Cell biology and regenerative Medicine Stanford University School of MedicineStanfordCAUSA

Nitric oxide is an important mediator of vascular autoregulation and is involved in pathophysiological changes after acute neurological *** oxide is generated by nitric oxide synthases from the amino acid L-arginine.L-arginine can also serve as a substrate for arginases or lead to the generation of dimethylarginines,asymmetric dimethylarginine,and symmetric dimethylarginine,by *** dimethylarginine is an endogenous inhibitor of nitric oxide synthase and can lead to endothelial *** review discusses the role of L-arginine metabolism in patients suffering from acute and critical neurological disorders often requiring neuro-intensive care *** addressed in this review include intracerebral hemorrhage,aneurysmal subarachnoid hemorrhage,and traumatic brain *** therapeutic advances in the field are described including current randomized controlled trials for traumatic brain injuries and hemorrhagic stroke.

关键词： arginine brain injuries,traumatic cerebral hemorrhage dimethylarginine nitric oxide stroke subarachnoid hemorrhage

CD9 role in proliferation, rejuvenation, and therapeutic applications

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Genes & Diseases 2024年第3期11卷 95-97页

作者： Sai Priyanka Kodam Neda Baghban Mujib Ullah Institutefor Immunityand Transplantation Stem Cell Biology and Regenerative MedicineSchool of MedicineMolecular Medicine Department of MedicineStanford UniversityPaloAltoCA94304USA

The CD9 gene,also known as the Tspan29 gene,codes for a protein called CD9,which is a member of the tetraspanin family of transmembrane proteins.^(1) The CD9 protein is involved in various cellular processes,including cell proliferation,differentiation,adhesion,and migration.^(1,2) CD9 has also been found to play a role in the regulation of stem cell proliferation and differentiation.

关键词： migration. therapeutic CD9

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

L1 drives HSC aging and affects prognosis of chronic myelomonocytic leukemia

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Signal Transduction and Targeted Therapy 2020年第1期5卷 774-777页

作者： Ying Wang Jin-ping Zheng Ying Luo Junyi Wang Lingjie Xu Jinyong Wang John M.Sedivy Zhangfa Song Hu Wang Zhenyu Ju Key Laboratory of Aging and Cancer biology of Zhejiang Province Institute of Aging ResearchSchool of MedicineHangzhou Normal UniversityHangzhou 311121China department of Public Health and Preventive Medicine Changzhi Medical CollegeChangzhiShanxi 046000P.R.China Key Laboratory of regenerative Medicine of Ministry of Education Guangzhou Regenerative Medicine and Health Guangdong LaboratoryInstitute of Aging and Regenerative MedicineJinan UniversityGuangzhou 510632China CAS Key Laboratory of regenerative biology and Guangdong Provincial Key Laboratory of Stem Cell and regenerative Medicine Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina department of Molecular biology Cell Biology and BiochemistryBrown UniversityProvidenceRI 02903USA department of Colorectal Surgery Sir Run Run Shaw HospitalZhejiang UniversityHangzhouChina

Dear Editor,Telomere attrition is one of the hallmark of *** Terc knockout mice exhibit impaired hematopoiesis,1 while the underling mechanisms remain poorly *** long interspersed element-1(L1)is the only human retrotransposable elements capable of autonomous retrotransposition,and evolutionarily *** studies reported that L1 is derepressed during the aging process with redistribution and reorganization of the heterochromatin.2 Considering that telomere shortening can cause chromosome instability and rearrangements,3 we speculate that L1 may play a role in impaired hematopoiesis in telomere dysfunctional mice.

关键词： impaired aging autonomous