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Zoological Research 2023年第3期44卷 577-590页

作者： Wenjuan Zhu Cecilia W.Lo The Chinese University of Hong Kong Hong Kong SARChina Department of Developmental Biology University of Pittsburgh School of MedicinePittsburghPA15201 USA Kunming Institute of Zoology-The Chinese University of Hong Kong(KIZ-CUHK)Joint Laboratory of Bioresources and Molecular Research of Common Diseases Hong Kong SARChina

Congenital heart disease(CHD)is observed in up to 1%of live births and is one of the leading causes of mortality from birth defects.While hundreds of genes have been implicated in the genetic etiology of CHD,their role in CHD pathogenesis is still poorly understood.This is largely a reflection of the sporadic nature of CHD,as well as its variable expressivity and incomplete penetrance.We reviewed the monogenic causes and evidence for oligogenic etiology of CHD,as well as the role of de novo mutations,common variants,and genetic modifiers.For further mechanistic insight,we leveraged single-cell data across species to investigate the cellular expression characteristics of genes implicated in CHD in developing human and mouse embryonic hearts.Understanding the genetic etiology of CHD may enable the application of precision medicine and prenatal diagnosis,thereby facilitating early intervention to improve outcomes for patients with CHD.

关键词： Congenital heart disease Genetic modifier single cell sequencing De novo mutation Protective variant Common copy number variant

System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer

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Oncology Research 2023年第4期31卷 591-604页

作者： TIANMING SHI RONGRONG YAN MI HAN Department of Gynecologic Oncology The International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Embryo Original Diseases School of MedicineShanghai Jiao Tong UniversityShanghaiChina

Ovarian cancer(OV)is highly heterogeneous tumor with a very poor prognosis.Studies increasingly show that T cell exhaustion is prognostically relevant in OV.The aim of this study was to dissect the heterogeneity of T cell subclusters in OV through single cell transcriptomic analysis.The single RNA-sequencing(scRNA-seq)data of five OV patients were analyzed,and six major cell clusters were identified after threshold screening.Further clustering of T cell-associated clusters revealed four subtypes.Pathways related to oxidative phosphorylation,G2M checkpoint,JAK-STAT and MAPK signaling were significantly activated,while the p53 pathway was inhibited in the CD8+exhausted T cells.The standard marker genes of CD8+T cell exhaustion were screened to develop a T-cell related gene score(TRS)based on random forest plots in TCGA cohort.The patients with low TRS have better prognosis compared to the patients with high TRS in both TCGA and GEO.In addition,most genes included in the TRS showed significant differences in expression levels between the high-and low-risk groups.Immune cell infiltration was analyzed using the MCPcounter and xcell algorithms,which revealed significant differences between the two risk groups,indicating that the different prognoses may stem from the respective immune landscapes.In addition,CD38 knockdown in OV cell lines increased apoptosis and inhibited invasion in vitro.Finally,we performed a drug sensitivity analysis and identified six potential drug candidates for OV.To summarize,we identified the heterogeneity and clinical significance of T cell exhaustion in OV and built a superior prognostic model based on T cell exhaustion genes,which can contribute to the development of more precise and effective therapies.

关键词： CD8+T exhausted Ovarian cancer Prognostic model single cell sequencing

single-cell transcriptome reveals core cell populations and androgen-RXFP2 axis involved in deer antler full regeneration

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cell Regeneration 2022年第1期11卷 449-467页

作者： Hengxing Ba Xin Wang Datao Wang Jing Ren Zhen Wang Hai-Xi Sun Pengfei Hu Guokun Zhang Shengnan Wang Chao Ma Yusu Wang Enpeng Wang Liang Chen Tianbin Liu Ying Gu Chunyi Li Institute of Antler Science and Product Technology Changchun Sci-Tech UniversityChangchun 130600China Jilin Provincial Key Laboratory of Deer Antler Biology Changchun 130600China BGI-Shenzhen Shenzhen 518083GuangdongChina Hubei Key Laboratory of cell Homeostasis College of Life SciencesRNA InstituteWuhan UniversityWuhanChina Institute of Special Wild Economic Animals and Plants Chinese Academy of Agricultural Sciences130112ChangchunChina Jilin Ginseng Academy Changchun University of Chinese MedicineChangchun 130117China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China Guangdong Provincial Key Laboratory of Genome Read and Write BGI-ShenzhenShenzhen 518120GuangdongChina College of Chinese Medicinal Materials Jilin Agricultural UniversityChangchun 130118China

Deer antlers constitute a unique mammalian model for the study of both organ formation in postnatal life and annual full regeneration.Previous studies revealed that these events are achieved through the proliferation and differentiation of antlerogenic periosteum(AP)cells and pedicle periosteum(PP)cells,respectively.As the cells resident in the AP and the PP possess stem cell attributes,both antler generation and regeneration are stem cell-based processes.However,the cell composition of each tissue type and molecular events underlying antler development remain poorly characterized.Here,we took the approach of single-cell RNA sequencing(scRNA-Seq)and identified eight cell types(mainly THY1^(+)cells,progenitor cells,and osteochondroblasts)and three core subclusters of the THY1^(+)cells(SC2,SC3,and SC4).Endothelial and mural cells each are heterogeneous at transcriptional level.It was the proliferation of progenitor,mural,and endothelial cells in the activated antler-lineage-specific tissues that drove the rapid formation of the antler.We detected the differences in the initial differentiation process between antler generation and regeneration using pseudotime trajectory analysis.These may be due to the difference in the degree of stemness of the AP-THY1+and PP-THY1^(+)cells.We further found that androgen-RXFP2 axis may be involved in triggering initial antler full regeneration.Fully deciphering the cell composition for these antler tissue types will open up new avenues for elucidating the mechanism underlying antler full renewal in specific and regenerative medicine in general.

关键词： Antler THY1+cell Generation Regeneration Core cell population Androgen-RXFP2 axis single cell sequencing

Organoid research on human early development and beyond

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Medical Review 2022年第5期2卷 512-523页

作者： Lu Wen Fuchou Tang Biomedical Pioneering Innovation Center Beijing Advanced Innovation Center for GenomicsSchool of Life SciencesPeking UniversityNO.5 Yiheyuan RoadBeijing 100871China

The organoid field has been developing rapidly during the last decade.Organoids for human pre-,peri-and post-implantation development have opened an avenue to study these biological processes in vitro,which have been hampered by lack of accessible research models for long term.The technologies of four fields,single cell omics sequencing,genome editing and lineage tracing,micro-fluidics and tissue engineering,have fueled the rapid development of the organoid field.In this review,we will discuss the organoid research on human early development as well as future directions of the organoid field combining with other powerful technologies.

关键词： genome editing implantation microfluidics organoid single cell sequencing tissue engineering

Emerging approaches and technologies in transplantation:the potential game changers

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cellular & Molecular Immunology 2019年第4期16卷 334-342页

作者： Anil Dangi Shuangjin Yu Xunrong Luo Division of Nephrology Department of MedicineDuke University Medical CenterDurhamNCUSA Duke Transplant Center Duke University Medical CenterDurhamNCUSA

Newly emerging technologies are rapidly changing conventional approaches to organ transplantation.In the modern era,the key challenges to transplantation include(1)how to best individualize and possibly eliminate the need for life-long immunosuppression and(2)how to expand the donor pool suitable for human transplantation.This article aims to provide readers with an updated review of three new technologies that address these challenges.First,single-cell RNA sequencing technology is rapidly evolving and has recently been employed in settings related to transplantation.The new sequencing data indicate an unprecedented cellular heterogeneity within organ transplants,as well as exciting new molecular signatures involved in alloimmune responses.Second,sophisticated nanotechnology platforms provide a means of therapeutically delivering immune modulating reagents to promote transplant tolerance.Tolerogenic nanoparticles with regulatory molecules and donor antigens are capable of targeting host immune responses with tremendous precision,which,in some cases,results in donor-specific tolerance.Third,CRISPR/Cas9 gene editing technology has the potential to precisely remove immunogenic molecules while inserting desirable regulatory molecules.This technology is particularly useful in generating genetically modified pigs for xenotransplantation to solve the issue of the shortage of human organs.Collectively,these new technologies are positioning the transplant community for major breakthroughs that will significantly advance transplant medicine.

关键词： Transplantation single cell sequencing Crisper Cas9 Nanotechnology

single cell metabolic phenome and genome via the ramanome technology platform:Precision medicine of infectious diseases at the ultimate precision?

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智能检验医学(英文) 2023年第1期1卷 5-14页

作者： Jian Xu Jianzhong Zhang Yingchun Xu Yi‐Wei Tang Bo Ma Yuzhang Wu single‐cell Center Qingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of SciencesQingdaoShandongChina State Key Laboratory of Infectious Disease Prevention and Control Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Department of Clinical Laboratory Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Medical Affairs Danaher Corporation/CepheidShanghaiChina Qingdao single‐cell Biotech.Co. Ltd.QingdaoShandongChina Chongqing International Institute of Immunology ChongqingSichuanChina

Due to the limitations of existing approaches,a rapid,sensitive,accurate,comprehensive,and generally applicable strategy to diagnose and treat bacterial and fungal infections remains a major challenge.Here,based on the ramanome technology platform,we propose a culture‐free,one cell resolution,phenome‐genome‐combined strategy called single‐cell identification,viability and vitality tests and source tracking(SCIVVS).For each cell directly extracted from a clinical specimen,the fingerprint region of the D2O‐probed single cell Raman spectrum(SCRS)enables species‐level identification based on a reference SCRS database of pathogen species,whereas the C‐D band accurately quantifies viability,metabolic vitality,phenotypic susceptibility to antimicrobials,and their intercellular heterogeneity.Moreover,to source track a cell,Raman‐activated cell sorting followed by sequencing or cultivation proceeds,producinging an indexed,high coverage genome assembly or a pure culture from precisely one pathogenic cell.Finally,an integrated SCIVVS workflow that features automated profiling and sorting of metabolic and morphological phenomes can complete the entire process in only a few hours.Because it resolves heterogeneity for both the metabolic phenome and genome,targets functions,can be automated,and is orders‐of‐magnitude faster while cost‐effective,SCIVVS is a new technological and data framework to diagnose and treat bacterial and fungal infections in various clinical and disease control settings.

关键词： diagnosis of microbial infections phenome ramanome Raman‐activated cell sorting(RACS) single cell sequencing

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Journal of Electronic Science and Technology 2021年第1期19卷 1-5页

作者： Zi-Wei Wang Chi-Chang Chang Quan Zou The Institute of Fundamental and Frontier Sciences University of Electronic Science and Technology of ChinaChengdu 610054 the School of Medical Informatics Chung Shan Medical UniversityTaichuang 40201 Medical University Hospital Taichung 40201

The outbreak of coronavirus disease 2019(COVID-2019)has drawn public attention all over the world.As a newly emerging area,single cell sequencing also exerts its power in the battle over the epidemic.In this review,the up-to-date knowledge of COVID-19 and its receptor is summarized,followed by a collection of the mining of single cell transcriptome profiling data for the information in aspects of the vulnerable cell types in humans and the potential mechanisms of the disease.

关键词： Coronavirus disease 2019(COVID-19) bioinformatics data mining single cell sequencing

Epigenetic regulations of gene expression in human germline cells

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Epigenetic regulations of gene expression in human germline ...

Cone Photoreceptor Circuitry and Development

中国生物化学与分子生物学会2016年全国学术会议

作者：汤富酬 BIOPIC College of Life Sciences Peking University

Measuring gene expression in individual cells is crucial for understanding the gene regulatory network controlling human embryonic development. We applied single-cell RNA-Seq analysis to human preimplantation embryos, primordial germ cells(PGCs), and human embryonic stem cells(h ESCs). We also systematically profiled the DNA methylome of human early embryos from the zygotic stage through to post-implantation. We showed that the major wave of genome-wide demethylation is complete at the 2-cell stage, contrary to previous observations in mice. Moreover, the demethylation of the paternal genome was much faster than that of the maternal genome, and by the end of the zygotic stage the genome-wide methylation level in male pronuclei was already lower than that in female pronuclei. Then we also showed that long interspersed nuclear elements(LINEs) or short interspersed nuclear elements(SINEs) that were evolutionarily young are demethylated to a milder extent compared to older elements in the same family and had higher abundance of transcripts, indicating that early embryos tend to retain higher residual methylation at the evolutionarily younger and more active transposable elements. Furthermore, we analyzed the DNA methylome of human PGCs and found global demethylation of their genomes. Approximately 10 to 11 weeks after gestation, the PGCs were nearly devoid of any DNA methylation, whereas the repeat elements still kept high level of residual methylation. Our work provides insights of critical features of the transcriptome and DNA methylome landscapes of human early embryos and primordial germ cells, as well as the functional significance of DNA methylome to regulation of gene expression and repression of transposable elements.

关键词： single cell functional genomics primordial germ cells DNA methylome single cell sequencing

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Cone Photoreceptor Circuitry and Development