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      Construction of a cross-species cell landscape at single-cell level

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          Abstract

          Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal—Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging.

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          Graphical Abstract

          Construction of a cross-species cell landscape at the single-cell level and revealing signatures and common pathways that changed throughout the life cycle.

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          STAR: ultrafast universal RNA-seq aligner.

          Alexander Dobin, Carrie A. Davis, Felix Schlesinger … (2013)
          Accurate alignment of high-throughput RNA-seq data is a challenging and yet unsolved problem because of the non-contiguous transcript structure, relatively short read lengths and constantly increasing throughput of the sequencing technologies. Currently available RNA-seq aligners suffer from high mapping error rates, low mapping speed, read length limitation and mapping biases. To align our large (>80 billon reads) ENCODE Transcriptome RNA-seq dataset, we developed the Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure. STAR outperforms other aligners by a factor of >50 in mapping speed, aligning to the human genome 550 million 2 × 76 bp paired-end reads per hour on a modest 12-core server, while at the same time improving alignment sensitivity and precision. In addition to unbiased de novo detection of canonical junctions, STAR can discover non-canonical splices and chimeric (fusion) transcripts, and is also capable of mapping full-length RNA sequences. Using Roche 454 sequencing of reverse transcription polymerase chain reaction amplicons, we experimentally validated 1960 novel intergenic splice junctions with an 80-90% success rate, corroborating the high precision of the STAR mapping strategy. STAR is implemented as a standalone C++ code. STAR is free open source software distributed under GPLv3 license and can be downloaded from http://code.google.com/p/rna-star/.
          Article 0 comments Cited 16025 times – based on 0 reviews     Review now
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            Comprehensive Integration of Single-Cell Data

            Tim Stuart, Andrew Butler, Paul Hoffman … (2019)
            Single-cell transcriptomics has transformed our ability to characterize cell states, but deep biological understanding requires more than a taxonomic listing of clusters. As new methods arise to measure distinct cellular modalities, a key analytical challenge is to integrate these datasets to better understand cellular identity and function. Here, we develop a strategy to "anchor" diverse datasets together, enabling us to integrate single-cell measurements not only across scRNA-seq technologies, but also across different modalities. After demonstrating improvement over existing methods for integrating scRNA-seq data, we anchor scRNA-seq experiments with scATAC-seq to explore chromatin differences in closely related interneuron subsets and project protein expression measurements onto a bone marrow atlas to characterize lymphocyte populations. Lastly, we harmonize in situ gene expression and scRNA-seq datasets, allowing transcriptome-wide imputation of spatial gene expression patterns. Our work presents a strategy for the assembly of harmonized references and transfer of information across datasets.
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              The Hallmarks of Aging

              Carlos López-Otín, Maria Blasco, Linda Partridge … (2014)
              Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.
              Article 0 comments Cited 3895 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Renying Wang
                Peijing Zhang
                Jingjing Wang
                Lifeng Ma
                Weigao E
                Shengbao Suo
                Mengmeng Jiang
                Jiaqi Li
                Haide Chen
                Huiyu Sun
                Lijiang Fei
                Ziming Zhou
                Yincong Zhou
                Yao Chen
                Weiqi Zhang
                Xinru Wang
                Yuqing Mei
                Zhongyi Sun
                Chengxuan Yu
                Jikai Shao
                Yuting Fu
                Yanyu Xiao
                Fang Ye
                Xing Fang:
                ORCID: https://orcid.org/0000-0002-9823-9620
                Hanyu Wu
                Qile Guo
                Xiunan Fang
                Xia Li
                Xianzhi Gao
                Dan Wang
                Peng-Fei Xu:
                ORCID: https://orcid.org/0000-0002-7318-8548
                Rui Zeng
                Gang Xu
                Lijun Zhu
                Lie Wang
                Jing Qu
                Dan Zhang:
                ORCID: https://orcid.org/0000-0003-1295-4795
                Hongwei Ouyang
                He Huang
                Ming Chen
                Shyh-Chang NG
                Guang-Hui Liu:
                ORCID: https://orcid.org/0000-0001-9289-8177
                Guo-Cheng Yuan:
                ORCID: https://orcid.org/0000-0002-2283-4714
                Guoji Guo:
                ORCID: https://orcid.org/0000-0002-1716-4621
                Xiaoping Han
                Journal
                Journal ID (nlm-ta): Nucleic Acids Res
                Journal ID (iso-abbrev): Nucleic Acids Res
                Journal ID (publisher-id): nar
                Title: Nucleic Acids Research
                Publisher: Oxford University Press
                ISSN (Print): 0305-1048
                ISSN (Electronic): 1362-4962
                Publication date Collection: 25 January 2023
                Publication date (Electronic): 05 August 2022
                Publication date PMC-release: 05 August 2022
                Volume: 51
                Issue: 2
                Pages: 501-516
                Affiliations
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Liangzhu Laboratory, Zhejiang University Medical Center , Hangzhou, 311121, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Liangzhu Laboratory, Zhejiang University Medical Center , Hangzhou, 311121, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Guangzhou Laboratory , Guangzhou 510005, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Liangzhu Laboratory, Zhejiang University Medical Center , Hangzhou, 311121, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Liangzhu Laboratory, Zhejiang University Medical Center , Hangzhou, 311121, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                College of Life Sciences, Zhejiang University , Hangzhou 310058, China
                Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310006, PR China
                CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, China National Center for Bioinformation , Beijing 100101, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University , Hangzhou 314400, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Institute of Immunology and Bone Marrow Transplantation Center, First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou 310058, China
                Women's Hospital, and Institute of Genetics, Zhejiang University School of Medicine , Hangzhou 310058, China
                Women's Hospital, and Institute of Genetics, Zhejiang University School of Medicine , Hangzhou 310058, China
                Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430030, China
                Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan 430030, China
                Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou 310058, China
                Institute of Immunology and Bone Marrow Transplantation Center, First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou 310058, China
                Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101, China
                Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310006, PR China
                Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University , Hangzhou 314400, China
                Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine , Hangzhou, Zhejiang 310058, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                College of Life Sciences, Zhejiang University , Hangzhou 310058, China
                Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101, China
                Institute for Stem Cell and Regeneration, Chinese Academy of Sciences , Beijing 100101, China
                Department of Genetics and Genomic Sciences, Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai , NY, NY 10029, USA
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Liangzhu Laboratory, Zhejiang University Medical Center , Hangzhou, 311121, China
                Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University , Hangzhou 314400, China
                Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine , Hangzhou, Zhejiang 310058, China
                Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, Zhejiang 310000, China
                Zhejiang Provincial Key Lab for Tissue Engineering and Regenerative Medicine, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine , Hangzhou, Zhejiang 310058, China
                Author notes
                To whom correspondence should be addressed. Xiaoping Han. Email: xhan@ 123456zju.edu.cn
                Correspondence may also be addressed to Guoji Guo. Email: ggj@ 123456zju.edu.cn
                Correspondence may also be addressed to Guo-Cheng Yuan. Email: guo-cheng.yuan@ 123456mssm.edu
                Correspondence may also be addressed to Guang-Hui Liu. Email: ghliu@ 123456ioz.ac.cn
                Correspondence may also be addressed to Shyh-Chang NG. Email: huangsq@ 123456ioz.ac.cn
                Correspondence may also be addressed to Peijing Zhang. Email: zhangpj@ 123456zju.edu.cn

                The authors wish it to be known that, in their opinion, the first eight authors should be regarded as Joint First Authors.

                Author information
                https://orcid.org/0000-0002-9823-9620
                https://orcid.org/0000-0002-7318-8548
                https://orcid.org/0000-0003-1295-4795
                https://orcid.org/0000-0001-9289-8177
                https://orcid.org/0000-0002-2283-4714
                https://orcid.org/0000-0002-1716-4621
                Article
                Publisher ID: gkac633
                DOI: 10.1093/nar/gkac633
                PMC ID: 9881150
                PubMed ID: 35929025
                SO-VID: 5c81d853-99ac-4181-9f4e-d3a18176c701
                Copyright © © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                Date accepted : 20 July 2022
                Date revision received : 30 June 2022
                Date received : 01 May 2022
                Page count
                Pages: 16
                Funding
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 31922049
                Award ID: 31930028
                Award ID: 32000461
                Funded by: National Key Research and Development Program, DOI 10.13039/501100012166;
                Award ID: 2018YFA0800503
                Categories
                Subject: AcademicSubjects/SCI00010
                Subject: NAR Breakthrough Article

                ScienceOpen disciplines: Genetics
                Data availability:
                ScienceOpen disciplines: Genetics

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