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Complete reprogramming to all-iPS mice

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Protein & Cell 2010年第1期1卷 2-3页

作者： Steven Y Cheng department of developmental genetics and center for regenerative medicine Nanjing Medical UniversityNanjing 210029China

The landmark discoveries by Shinya Yamanaka in mice and later separately by James Thompson in humans that adult animal cells can be reprogrammed to a pluripotent state of embryonic stem(ES)cells by forced expression of just a few key transcription factors have permanently altered a long-held view about the stability of differentiated cells in developmental biology,and suggested a way of generating personalized replacement tissues from patients’own cells for the regenerative medical treatment.

关键词： programming generating permanent

Insulin, longevity, and genetic analysis of metabolism

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Protein & Cell 2010年第7期1卷 605-606页

作者： Steven Y Cheng department of developmental genetics center for regenerative medicine Nanjing Medical UniversityNanjing 210029China

In a 1989 Hollywood hit“Sex,Lies,and Videotapes”,director Steven Soderbergh told a story of an incestuous affair between a hot-shot lawyer and the sister of his married *** over-stayed visit by a drifter whose unusual fetish of videotaping conversations about sex lives of women deconvoluted this adulterous *** the biological life,persistent bias can also throw off a balance such as the homeostasis delicately constructed among metabolism,longevity,and the insulin signaling *** a recent paper published in Cell Metabolism,Yong Liu’s group at the Shanghai Institute of Nutritional Sciences and Liangyou Rui’s group at the University of Michigan Medical School reported that alteration of metabolism through genetic deletion of SH2B,a gene encoding an adaptor protein required for insulin signaling,causes significant changes in the life span of affected fruitflies and *** the manmade and the god-made stories show only a slight superficial analogy in form,they both unfold through serendipitous analyses of seemingly unrelated events,a theme that reoccurringly underscores the importance of basic research.

关键词： metabolism analogy conversation

Battle of the sexes: contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis

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Asian Journal of Andrology 2019年第3期21卷 260-269页

作者： Yun-Fai Chris Lau Yunmin Li Tatsuo Kido Division of Cell and developmental genetics Department of Medicine VA Medical Center and Institute for Human Genetics University of California San Francisco CA 94121 USA

The Y-located testis-specific protein Y-encoded (TSPY) and its X-homologue TSPX originated from the same ancestral gene, but act as a proto-oncogene and a tumor suppressor gene, respectively. TSPY has specialized in male-specific functions, while TSPX has assumed the functions of the ancestral gene. Both TSPY and TSPX harbor a conserved SET/NAP domain, but are divergent at flanking structures. Specifically, TSPX contains a C-terminal acidic domain, absent in TSPY. They possess contrasting properties, in which TSPY and TSPX, respectively, accelerate and arrest cell proliferation, stimulate and inhibit cyclin B-CDK1 phosphorylation activities, have no effect and promote proteosomal degradation of the viral HBx oncoprotein, and exacerbate and repress androgen receptor (AR) and constitutively active AR variant, such as AR-V7, gene transactivation. The inhibitory domain has been mapped to the carboxyl acidic domain in TSPX, truncation of which results in an abbreviated TSPX exerting positive actions as TSPY. Transposition of the acidic domain to the C-terminus of TSPY results in an inhibitory protein as intact TSPX. Hence, genomic mutations/aberrant splicing events could generate TSPX proteins with truncated acidic domain and oncogenic properties as those for TSPY. Further, TSPY is upregulated by AR and AR-V7 in ligand-dependent and ligand-independent manners, respectively, suggesting the existence of a positive feedback loop between a Y-located proto-oncogene and male sex hormone/receptors, thereby amplifying the respective male oncogenic actions in human cancers and diseases. TSPX counteracts such positive feedback loop. Hence, TSPY and TSPX are homologues on the sex chromosomes that function at the two extremes of the human oncogenic spectrum.

关键词： androgen receptor AR-V7 cell cycle regulation cyclin B-CDK1 oncogene sex chromosomes sex differences TSPX TSPY tumor suppressor

Roles of the Y chromosome genes in human cancers

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Asian Journal of Andrology 2015年第3期17卷 373-380页

作者： Tatsuo Kido Yun-Fai Chris Lau Division of Cell and developmental genetics Department of Medicine Veterans Affairs Medical Center Institute for Human Genetics University of California San Francisco California 94121 USA

Male and female differ genetically by their respective sex chromosome composition, that is, XY as male and XX as female. Although both X and Y chromosomes evolved from the same ancestor pair of autosomes, the Y chromosome harbors male-specific genes, which play pivotal roles in male sex determination, germ cell differentiation, and masculinization of various tissues. Deletions or translocation of the sex-determining gene, SRY, from the Y chromosome causes disorders of sex development （previously termed as an intersex condition） with dysgenic gonads. Failure of gonadal development results not only in infertility, but also in increased risks of germ cell tumor （GCT）, such as gonadoblastoma and various types of testicular GCT. Recent studies demonstrate that either loss of Y chromosome or ectopic expression of Y chromosome genes is closely associated with various male-biased diseases, including selected somatic cancers. These observations suggest that the Y-linked genes are involved in male health and diseases in more frequently than expected. Although only a small number of protein-coding genes are present in the male-specific region of Y chromosome, the impacts of Y chromosome genes on human diseases are still largely unknown, due to lack of in vivo models and differences between the Y chromosomes of human and rodents. In this review, we highlight the involvement of selected Y chromosome genes in cancer development in men.

关键词： germ cell tumors RBMY, Y-linked somatic cancers TSPY Y chromosome

AIAP: A Quality Control and Integrative Analysis Package to Improve ATAC-seq Data Analysis

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Genomics, Proteomics & Bioinformatics 2021年第4期19卷 641-651页

作者： Shaopeng Liu Daofeng Li Cheng Lyu Paul MGontarz Benpeng Miao Pamela A.F.Madden Ting Wang Bo Zhang department of developmental Biology Center of Regenerative MedicineWashington University School of MedicineSt.LouisMO 63108USA department of genetics Center for Genomic Sciences and Systems BiologyWashington University School of MedicineSt.LouisMO 63108USA department of Psychiatry Washington University School of MedicineSt.LouisMO 63108USA

Assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq) is a technique widely used to investigate genome-wide chromatin accessibility. The recently published Omni-ATAC-seq protocol substantially improves the signal/noise ratio and reduces the input cell number. High-quality data are critical to ensure accurate *** tools have been developed for assessing sequencing quality and insertion size distribution for ATAC-seq data;however, key quality control(QC) metrics have not yet been established to accurately determine the quality of ATAC-seq data. Here, we optimized the analysis strategy for ATAC-seq and defined a series of QC metrics for ATAC-seq data,including reads under peak ratio(RUPr), background(BG), promoter enrichment(Pro En), subsampling enrichment(Sub En), and other measurements. We incorporated these QC tests into our recently developed ATAC-seq Integrative Analysis Package(AIAP) to provide a complete ATAC-seq analysis system, including quality assurance, improved peak calling, and downstream differential analysis. We demonstrated a significant improvement of sensitivity(20%–60%) in both peak calling and differential analysis by processing paired-end ATAC-seq datasets using AIAP. AIAP is compiled into Docker/Singularity, and it can be executed by one command line to generate a comprehensive QC report. We used ENCODE ATAC-seq data to benchmark and generate QC recommendations, and developed q ATACViewer for the userfriendly interaction with the QC report. The software, source code, and documentation of AIAP are freely available at https://***/Zhang-lab/ATAC-seq_QC_analysis.

关键词： ATAC-seq Quality control Chromatin accessibility Differential analysis Data visualization

Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

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World Journal of Methodology 2025年第1期15卷 72-79页

作者： Serdar Kabatas ErdinçCivelek Eyüp Can Savrunlu Umut Karaaslan Özlem Yıldız Erdal Karaöz department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye department of Pediatric Allergy-Immunology Institute of Health Sciences Marmara UniversityIstanbul 34865Türkiye center for Stem Cell&Gene Therapy Research and Practice University of Health Sciences TurkeyIstanbul 34255Türkiye department of Child and Adolescent Psychiatry University of Health SciencesGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye department of Child and Adolescent Psychiatry Kocaeli University Faculty of MedicineKocaeli 41001Türkiye center for regenerative medicine and Stem Cell Research&Manufacturing Liv HospitalIstanbul 34340Türkiye department of Histology and Embryology Istinye UniversityFaculty of MedicineIstanbul 34010Türkiye center for Stem Cell and Tissue Engineering Research and Practice Istinye UniversityIstanbul 34340Türkiye

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted *** recent studies,neuroinflammation and immune dysregulation have come to the forefront in its *** are studies suggesting that stem cell therapy may be effective in the treatment of *** To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell *** A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with *** The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 developmental Screening Test),especially in language and gross motor *** serious side effects were encountered during the 2-year *** The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

关键词： Autism spectrum disorder Neurorehabilitation Stem cell transplantation Wharton jelly mesenchymal stem cells Inflammation

The role of microRNAs during the genesis of medulloblastomas induced by the hedgehog pathway

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The Journal of Biomedical Research 2011年第1期25卷 42-48页

作者： Steven Y Cheng department of developmental genetics and center for regenerative medicine Nanjing Medical University

Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the role of miRNAs during the genesis of MB induced by sustained Hh activation. In the primary screening, we used stemloop RT-PCR to test the expression of 90 different miRNAs in the wildtype （WT） and Ptc-/- MEF cell lines. In the secondary screening, the miRNAs screened from the first screening were validated in the Sufu-/- MEF cell lines. We then verified the expression of miRNAs both in the normal cerebellar tissues and the MB induced by activated Hh pathway, and examined the expression of the other 21 miRNA members of the miR-154 cluster in the MB and normal cerebellum. In the first screening, 13 miRNAs showed significant differential expression in WT and Ptc-/- MEF cell lines, while 10 of them had significant difference in the Sufu-/- MEF cell line. Compared to the normal mouse cerebellum, only 2 miRNAs in 15 miRNAs were differentially expressed between the MB and normal cerebellar tissues. Among 21 members of the miR-154 cluster, 6 miRNAs were downregulated in the MB. Our study demonstrated that miR-154 may be regulated by the Hh pathway, and the activation of the Hh pathway led to the downregulation of the miR-154 cluster, resulting in the genesis of MB.

关键词： Hedgehog signaling pathway microRNAs miR-154 cluster medulloblastomas

Review and Evaluate the Bioinformatics Analysis Strategies of ATAC-seq and CUT&Tag Data

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Genomics, Proteomics & Bioinformatics 2024年第3期22卷 11-27页

作者： Siyuan Cheng Benpeng Miao Tiandao Li Guoyan Zhao Bo Zhang department of developmental Biology Center of Regenerative MedicineWashington University School of MedicineSt.LouisMO 63108USA department of genetics Washington University School of MedicineSt.LouisMO 63108USA department of Neurology Washington University School of MedicineSt.LouisMO 63108USA department of Pathology and Immunology Washington University School of MedicineSt.LouisMO 63108USA

Efficient and reliable profiling methods are essential to study ***5,one of the first identified prokaryotic transposases with high DNA-binding and tagmentation efficiency,is widely adopted in different genomic and epigenomic protocols for high-throughputly exploring the genome and *** on Tn5,the Assay for Transposase-Accessible Chromatin using sequencing(ATAC-seq)and the Cleavage Under Targets and Tagmentation(CUT&Tag)were developed to measure chromatin accessibility and detect DNA–protein *** methodologies can be applied to large amounts of biological samples with low-input levels,such as rare tissues,embryos,and sorted single ***,fast and proper processing of these epigenomic data has become a bottleneck because massive data production continues to increase ***,inappropriate data analysis can generate biased or misleading ***,it is essential to evaluate the performance of Tn5-based ATAC-seq and CUT&Tag data processing bioinformatics tools,many of which were developed mostly for analyzing chromatin immunoprecipitation followed by sequencing(ChIP-seq)***,we conducted a comprehensive benchmarking analysis to evaluate the performance of eight popular software for processing ATAC-seq and CUT&Tag *** compared the sensitivity,specificity,and peak width distribution for both narrow-type and broad-type peak *** also tested the influence of the availability of control IgG input in CUT&Tag data ***,we evaluated the differential analysis strategies commonly used for analyzing the CUT&Tag *** study provided comprehensive guidance for selecting bioinformatics tools and recommended analysis strategies,which were implemented into Docker/Singularity images for streamlined data analysis.

关键词： Tn5 transposase Epigenetic Bioinformatics ATAC-seq CUT&Tag

Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9

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Bone Research 2015年第3期3卷 140-151页

作者： Anat Kohn Timothy P Rutkowski Zhaoyang Liu Anthony J Mirando Michael J Zuscik Regis J O'Keefe Matthew J Hilton department of Orthopaedics and Rehabilitation The Center for Musculoskeletal Research University of Rochester Medical Center department of Biomedical genetics University of Rochester Medical Center department of Biology University of Rochester department of Orthopaedic Surgery Duke Orthopaedic Cellular Developmental and Genome Laboratories Duke University School of Medicine department of Orthopaedic Surgery Washington University School of Medicine

RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, although how this occurs at the molecular level in chondrocytes and whether this transcriptional regulation mediates Notch control of chondrocyte hypertrophy and cartilage development is unknown or controversial. Here we have provided conclusive genetic evidence linking RBPjk-dependent Notch signaling to the regulation of Sox9 expression and chondrocyte hypertrophy by examining tissuespecific Rbpjk mutant（Prx1Cre;Rbpjkf/f）, Rbpjk mutant/Sox9 haploinsufficient（Prx1Cre;Rbpjkf/f;Sox9f/1）,and control embryos for alterations in SOX9 expression and chondrocyte hypertrophy during cartilage development. These studies demonstrate that Notch signaling regulates the onset of chondrocyte maturation in a SOX9-dependent manner, while Notch-mediated regulation of terminal chondrocyte maturation likely functions independently of SOX9. Furthermore, our in vitro molecular analyses of the Sox9 promoter and Notch-mediated regulation of Sox9 gene expression in chondrogenic cells identified the ability of Notch to induce Sox9 expression directly in the acute setting, but suppresses Sox9 transcription with prolonged Notch signaling that requires protein synthesis of secondary effectors.

关键词： Figure Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9 NICD SOX