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Inhibition of Wnt activity improves peri-implantation development of somatic cell nuclear transfer embryos

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National Science Review 2023年第9期10卷 163-179页

作者： Yanhe Li Caihong Zheng Yingdong Liu Jincan He Qiang Zhang Yalin Zhang Xiaochen Kou Yanhong Zhao Kuisheng Liu Dandan Bai Yanping Jia Xiaoxiao Han Yifan Sheng Jiqing Yin Hong Wang Shuai Gao Wenqiang Liu Shaorong Gao Shanghai key laboratory of Maternal Fetal medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyShanghai Key Laboratory of Signaling and Disease Research Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and Technology Tongji University CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of Genomics Chinese Academy of Sciences and China National Center for Bioinformation key laboratory of Animal Genetics Breeding and Reproduction of the MARA National Engineering Laboratory for Animal Breeding College of Animal Science and Technology China Agricultural University

Somatic cell nuclear transfer(SCNT) can reprogram differentiated somatic cells into totipotency.Although pre-implantation development of SCNT embryos has greatly improved,most SCNT blastocysts are still arrested at the peri-implantation stage,and the underlying mechanism remains elusive.Here,we develop a 3D in vitro culture system for SCNT peri-implantation embryos and discover that persistent Wnt signals block the naive-to-primed pluripotency transition of epiblasts with aberrant H3K27me3 occupancy,which in turn leads to defects in epiblast transformation events and subsequent implantation failure.Strikingly,manipulating Wnt signals can attenuate the pluripotency transition and H3K27me3 deposition defects in epiblasts and achieve up to a 9-fold increase in cloning efficiency.Finally,single-cell RNA-seq analysis reveals that Wnt inhibition marke dly enhances the lineage developmental trajectories of SCNT blastocysts during peri-implantation development.Overall,these findings reveal diminished potentials of SCNT blastocysts for lineage specification and validate a critical peri-implantation barrier for SCNT embryos.

关键词： SCNT reprogramming implantation Wnt naïve pluripotency primed pluripotency epiblast single-cell RNA-seq epigenetic barrier

Variation in the life history strategy underlies functional diversity of tumors

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National Science Review 2021年第2期8卷 32-42页

作者： Tao Li Jialin Liu Jing Feng Zhenzhen Liu Sixue Liu Minjie Zhang Yuezheng Zhang Yali Hou Dafei Wu Chunyan Li Yongbin Chen Hua Chen Xuemei Lu State key laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of Sciences CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences University of Chinese Academy of Sciences Beijing Advanced Innovation Center for Big Data-Based precision medicine School of Medicine and Engineering and Key Laboratory of Big Data-Based Precision Medicine(Ministry of Industry and Information Technology)Beihang University key laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of Zoology

Classical r-vs. K-selection theory describes the trade-offs between high reproductive output and competitiveness and guides research in evolutionary ecology. While its impact has waned in the recent past,cancer evolution may rekindle it. Herein, we impose r-or K-selection on cancer cell lines to obtain strongly proliferative r cells and highly competitive K cells to test ideas on life-history strategy evolution. RNA-seq indicates that the trade-offs are associated with distinct expression of genes involved in the cell cycle,adhesion, apoptosis, and contact inhibition. Both empirical observations and simulations based on an ecological competition model show that the trade-off between cell proliferation and competitiveness can evolve adaptively. When the r and K cells are mixed, they exhibit strikingly different spatial and temporal distributions. Due to this niche separation, the fitness of the entire tumor increases. The contrasting selective pressure may operate in a realistic ecological setting of actual tumors.

关键词： density-dependent selection trade-offs cancer cell phenotypic diversity competition

Circulating Tumor DNA as Biomarkers for CancerDetection

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genomics, Proteomics & Bioinformatics 2017年第2期15卷 59-72页

作者： Xiao Han Junyun Wang Yingli Sun CAS Key Laboratory of Genomic and Precision Medicine China Gastrointestinal Cancer Research Center Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China

Detection of circulating tumor DNAs(ct DNAs) in cancer patients is an important component of cancer precision medicine ct DNAs. Compared to the traditional physical and biochemical methods, blood-based ct DNA detection offers a non-invasive and easily accessible way for cancer diagnosis, prognostic determination, and guidance for treatment. While studies on this topic are currently underway, clinical translation of ct DNA detection in various types of cancers has been attracting much attention, due to the great potential of ct DNA as blood-based biomarkers for early diagnosis and treatment of cancers. ct DNAs are detected and tracked primarily based on tumorrelated genetic and epigenetic alterations. In this article, we reviewed the available studies on ct DNA detection and described the representative methods. We also discussed the current understanding of ct DNAs in cancer patients and their availability as potential biomarkers for clinical purposes. Considering the progress made and challenges involved in accurate detection of specific cell-free nucleic acids, ct DNAs hold promise to serve as biomarkers for cancer patients, and further validation is needed prior to their broad clinical use.

关键词： precision medicine Liquid biopsy Circulating tumor DNA Biomarker Clinical diagnosis Cell-free nucleic acids

An Old Story Retold: Loss of G1 Control Defines A Distinct genomic Subtype of Esophageal Squamous Cell Carcinoma

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genomics, Proteomics & Bioinformatics 2015年第4期13卷 258-270页

作者： Qiyan Wang Jian Bai Amir Abliz Ying Liu Kenan Gong Jingjing Li Wenjie Shi Yaqi Pan Fangfang Liu Shujuan Lai Haijun Yang Changdong Lu Lixin Zhang Wei Chen Ruiping Xu Hong Cai Yang Ke Changqing Zeng MOE key laboratory of Carcinogenesis and Translational Research Laboratory of Genetics Peking UniversityCancer Hospital & Institute Beijing University of Chinese medicine CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of Genomics Chinese Academy of Sciences University of Chinese Academy of Sciences Anyang Cancer Hospital

Esophageal squamous cell carcinoma （ESCC） has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exonic mutations and structural alterations. The clinical implications of these genetic alterations were also analyzed. Exome sequencing and verification were performed for nine pairs of ESCC and the matched blood samples, followed by validation with additional sam- ples using Sanger sequencing. Whole-genomc SNP arrays were employed to detect copy number alteration （CNA） and loss of heterozygosity （LOH） in 55 cases, including the nine ESCC samples subjected to exome sequencing. A total of 108 non-synonymous somatic mutations （NSSMs） in 102 genes were verified in nine patients. The chromatin modification process was found to be enriched in our gene ontology （GO） analysis. Tumor genomes with TP53 mutations were signifi- cantly more unstable than those without TP53 mutations. In terms of the landscape of genomic alterations, deletion of 9p21.3 covering CDKN2A/2B （30.9%）, amplification of 1 1q13.3 covering CCND1 （30.9%）, and TP53 point mutation （50.9%） occurred in two-thirds of the cases. These results suggest that the deregulation of the G1 phase during the cell cycle is a key event in ESCC. Furthermore, six minimal common regions were found to be significantly altered in ESCC samples and three of them, 9p21.3, 7p 11.2, and 3p 12.1, were associated with lymph node metastasis. With the high correlation of TP53 mutation and genomic instability in ESCC, the amplification of CCND1, the deletion of CDKN2A/2B, and the somatic mutation of TP53 appear to play pivotal roles via G1 deregulation and therefore helps to classify this cancer into different genomic subtypes. These findings provide clinical significance that could be useful in future molecular diagnoses and therapeutic targeting.

关键词： Esophageal squamous cell carcinoma genomic subtype somatic mutation Copy number alteration Cell cycle deregulation

The priming induction regimen of HAG as a low dose chemotherapy strategy in AML clonal evolution

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Science China(Life Sciences) 2015年第12期58卷 1302-1305页

作者： CHEN AiLi YANG JingYi HU ShaoYan WANG Qian-Fei key laboratory of genomic and precision medicine Beijing Institute of Genomics Chinese Academy of Sciences The Children's Hospital of Soochow University

Chemotherapy employs chemical substances to interfere with the growth of cancer cells,and is a major treatment strategy in human cancer including acute myeloid leukemia(AML).Although they often effectively kill fast-d... 详细信息

关键词：白血病进化策略化疗低剂量克隆诱导肿瘤细胞癌细胞

A Computational Approach for Modeling the Allele Frequency Spectrum of Populations with Arbitrarily Varying Size

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genomics, Proteomics & Bioinformatics 2019年第6期17卷 635-644页

作者： Hua Chen CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China cas Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunming 650223China School of Future Technology University of Chinese Academy of SciencesBeijing 100049China

The allele frequency spectrum(AFS), or site frequency spectrum, is commonly used to summarize the genomic polymorphism pattern of a sample, which is informative for inferring population history and detecting natural selection. In 2013, Chen and Chen developed a method for analytically deriving the AFS for populations with temporally varying size through the coalescence time-scaling function. However, their approach is only applicable to population history scenarios in which the analytical form of the time-scaling function is tractable. In this paper, we propose a computational approach to extend the method to populations with arbitrary complex varying size by numerically approximating the time-scaling function. We demonstrate the performance of the approach by constructing the AFS for two population history scenarios: the logistic growth model and the Gompertz growth model, for which the AFS are unavailable with existing approaches. Software for implementing the algorithm can be downloaded at http://***/software/.

关键词： Allele frequency spectrum Complex demography Population history Population genetic inference Coalescent

Genetic analysis and ecological niche modeling delimit species boundary of the Przewalski’s scorpion(Scorpiones: Buthidae) in arid Asian inland

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Zoological Systematics 2020年第2期45卷 81-96页

作者： Xueshu Zhang Gaoming Liu Yu Feng Dexing Zhang Chengmin Shi State key laboratory of Integrated Management of Pest Insects and Rodents Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China

Reliable delimitation of venomous scorpions is not only consequential to toxicological studies but also instructive to conservation and exploration of these important medical resources.In the present study,we delimited species boundary for the the Przewalski’s scorpion from arid northwest China through a combined approach employing phylogenetic analysis,ecological niche modeling and morphological comparison.Our results indicate that the Przewalski’s scorpion represent an independent taxonomic unit and should be recognized as full species rank,Mesobuthus przewalskii stat.nov.This species and the Chinese scorpion M.martensii represent the eastern members of the M.caucasicus species group which manifests a trans-Central Asia distribution across the Tianshan Mountains range.We also discussed the likely geographic barrier and climatic boundary that demarcate distributional range of the the Przewalski’s scorpion.

关键词： Mesobuthus species complex mitochondrial DNA ecological niche modeling distribution range

On the founder effect in COVID-19 outbreaks:how many infected travelers may have started them all?

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National Science Review 2021年第1期8卷 30-39页

作者： Yongsen Ruan Zhida Luo Xiaolu Tang Guanghao Li Haijun Wen Xionglei He Xuemei Lu Jian Lu Chung-I Wu State key laboratory of Biocontrol School of Life Sciences Sun Yat-sen University State key laboratory of Protein and Plant Gene Research Center for Bioinformatics School of Life SciencesPeking University CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of Genomics Chinese Academy of Sciences State key laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyCenter for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

How many incoming travelers（I;at time 0, equivalent to the ‘founders’ in evolutionary genetics） infected with SARS-CoV-2 who visit or return to a region could have started the epidemic of that region? I;would be informative about the initiation and progression of epidemics. To obtain I;, we analyze the genetic divergence among viral populations of different regions. By applying the ‘individual-output’ model of genetic drift to the SARS-CoV-2 diversities, we obtain I; 0） or the fitness of the variants. With such a tiny trickle of human movement igniting many outbreaks, the crucial stage of repressing an epidemic in any region should,therefore, be the very first sign of local contagion when positive cases first become identifiable. The implications of the highly ‘portable’ epidemics, including their early evolution prior to any outbreak, are explored in the companion study（Ruan et al., personal communication）.

关键词： SARS-CoV-2 COVID-19 population genetics genetic drift founder effect

Transcriptomic analysis reveals key regulators of mammogenesis and the pregnancy-lactation cycle

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Science China(Life Sciences) 2014年第3期57卷 340-355页

作者： ZHOU YuanYuan GONG Wei XIAO JingFa WU JiaYan PAN LinLin LI XiaoNuan WANG XuMin WANG WeiWei HU SongNian YU Jun Beijing key laboratory of Genome and precision medicine Technologies CAS Key Laboratory of Genome Sciences and InformationBeijing Institute of GenomicsChinese Academy of Sciences University of Chinese Academy of Sciences Division of Gastroenterology Department of MedicineUniversity of Alberta

An organ unique to mammals,the mammary gland develops 90%of its mass after birth and experiences the pregnancy-lactation-involution cycle(PL cycle)during reproduction.To understand mammogenesis at the transcriptomic level and using a ribo-minus RNA-seq protocol,we acquired greater than 50 million reads each for the mouse mammary gland during pregnancy(day 12 of pregnancy),lactation(day 14 of lactation),and involution(day 7 of involution).The pregnancy-,lactation-and involution-related sequencing reads were assembled into 17344,10160,and 13739 protein-coding transcripts and1803,828,and 1288 non-coding RNAs(ncRNAs),respectively.Differentially expressed genes(DEGs)were defined in the three samples,which comprised 4843 DEGs(749 up-regulated and 4094 down-regulated)from pregnancy to lactation and4926 DEGs(4706 up-regulated and 220 down-regulated)from lactation to involution.Besides the obvious and substantive upand down-regulation of the DEGs,we observe that lysosomal enzymes were highly expressed and that their expression coincided with milk secretion.Further analysis of transcription factors such as Trps1,Gtf2i,Tcf7l2,Nupr1,Vdr,Rb1,and Aebp1,and ncRNAs such as mir-125b,Let7,mir-146a,and mir-15 has enabled us to identify key regulators in mammary gland development and the PL cycle.

关键词：转录水平哺乳期周期怀孕差异表达基因非编码RNA 组分动物乳腺

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