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  1. Article ; Online: Characterization of alternative mRNA splicing in cultured cell populations representing progressive stages of human fetal kidney development.

    Wineberg, Yishay / Kanter, Itamar / Ben-Haim, Nissim / Pode-Shakked, Naomi / Bucris, Efrat / Bar-Lev, Tali Hana / Oriel, Sarit / Reinus, Harel / Yehuda, Yishai / Gershon, Rotem / Shukrun, Rachel / Bar-Lev, Dekel Dov / Urbach, Achia / Dekel, Benjamin / Kalisky, Tomer

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 19548

    Abstract: Nephrons are the functional units of the kidney. During kidney development, cells from the cap mesenchyme-a transient kidney-specific progenitor state-undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various ... ...

    Abstract Nephrons are the functional units of the kidney. During kidney development, cells from the cap mesenchyme-a transient kidney-specific progenitor state-undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various epithelial cell types that create the tubular structures of the nephron. Faults in this transition can lead to a pediatric malignancy of the kidney called Wilms' tumor that mimics normal kidney development. While human kidney development has been characterized at the gene expression level, a comprehensive characterization of alternative splicing is lacking. Therefore, in this study, we performed RNA sequencing on cell populations representing early, intermediate, and late developmental stages of the human fetal kidney, as well as three blastemal-predominant Wilms' tumor patient-derived xenografts. Using this newly generated RNAseq data, we identified a set of transcripts that are alternatively spliced between the different developmental stages. Moreover, we found that cells from the earliest developmental stage have a mesenchymal splice-isoform profile that is similar to that of blastemal-predominant Wilms' tumor xenografts. RNA binding motif enrichment analysis suggests that the mRNA binding proteins ESRP1, ESRP2, RBFOX2, and QKI regulate alternative mRNA splicing during human kidney development. These findings illuminate new molecular mechanisms involved in human kidney development and pediatric kidney cancer.
    MeSH term(s) Humans ; Child ; Alternative Splicing ; RNA, Messenger/genetics ; Wilms Tumor/genetics ; Wilms Tumor/pathology ; Kidney Neoplasms/pathology ; Kidney/pathology ; Cells, Cultured ; RNA Splicing Factors/genetics ; Repressor Proteins/genetics
    Chemical Substances RNA, Messenger ; RBFOX2 protein, human ; RNA Splicing Factors ; Repressor Proteins
    Language English
    Publishing date 2022-11-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-24147-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Macrophages restrict the nephrogenic field and promote endothelial connections during kidney development.

    Munro, David AD / Wineberg, Yishay / Tarnick, Julia / Vink, Chris S / Li, Zhuan / Pridans, Clare / Dzierzak, Elaine / Kalisky, Tomer / Hohenstein, Peter / Davies, Jamie A

    eLife

    2019  Volume 8

    Abstract: The origins and functions of kidney macrophages in the adult have been explored, but their roles during development remain largely unknown. Here we characterise macrophage arrival, localisation, heterogeneity, and functions during kidney organogenesis. ... ...

    Abstract The origins and functions of kidney macrophages in the adult have been explored, but their roles during development remain largely unknown. Here we characterise macrophage arrival, localisation, heterogeneity, and functions during kidney organogenesis. Using genetic approaches to ablate macrophages, we identify a role for macrophages in nephron progenitor cell clearance as mouse kidney development begins. Throughout renal organogenesis, most kidney macrophages are perivascular and express F4/80 and CD206. These macrophages are enriched for mRNAs linked to developmental processes, such as blood vessel morphogenesis. Using antibody-mediated macrophage-depletion, we show macrophages support vascular anastomoses in cultured kidney explants. We also characterise a subpopulation of galectin-3
    MeSH term(s) Animals ; Calcium-Binding Proteins/genetics ; Cell Lineage/genetics ; Galectin 3/genetics ; Gene Expression Regulation, Developmental ; Kidney/growth & development ; Kidney/metabolism ; Lectins, C-Type/genetics ; Macrophages/metabolism ; Mannose-Binding Lectins/genetics ; Mice ; Nephrons/growth & development ; Nephrons/metabolism ; Organogenesis/genetics ; Receptors, Cell Surface/genetics ; Receptors, G-Protein-Coupled/genetics ; Stem Cells/metabolism
    Chemical Substances Adgre1 protein, mouse ; Calcium-Binding Proteins ; Galectin 3 ; Lectins, C-Type ; Lgals3 protein, mouse ; Mannose-Binding Lectins ; Receptors, Cell Surface ; Receptors, G-Protein-Coupled ; mannose receptor
    Language English
    Publishing date 2019-02-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.43271
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A brief review of single-cell transcriptomic technologies

    Kalisky, Tomer / Bar-Lev, Tali Hana / Ben-Haim, Nissim / Gilad, Shlomit / Kanter, Itamar / Oriel, Sarit / Pyne, Saumyadipta / Trink, Ariel / Wineberg, Yishay

    Briefings in functional genomics. 2017 Sept. 01, v. 17, no. 1

    2017  

    Abstract: In recent years, there has been an effort to develop new technologies for measuring gene expression and sequence information from thousands of individual cells. Large data sets that were obtained using these ‘single cell’ technologies have allowed ... ...

    Abstract In recent years, there has been an effort to develop new technologies for measuring gene expression and sequence information from thousands of individual cells. Large data sets that were obtained using these ‘single cell’ technologies have allowed scientists to address fundamental questions in biomedicine ranging from stems cells and development to cancer and immunology. Here, we provide a brief review of recent developments in single-cell technology. Our intention is to provide a quick background for newcomers to the field as well as a deeper description of some of the leading technologies to date.
    Keywords data collection ; gene expression ; immunology ; medicine ; neoplasms ; technology ; transcriptomics
    Language English
    Dates of publication 2017-0901
    Size p. 64-76.
    Publishing place Oxford University Press
    Document type Article
    ZDB-ID 2540916-5
    ISSN 2041-2657 ; 2041-2649 ; 2041-2647
    ISSN (online) 2041-2657
    ISSN 2041-2649 ; 2041-2647
    DOI 10.1093/bfgp/elx019
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Single-Cell RNA Sequencing Reveals mRNA Splice Isoform Switching during Kidney Development.

    Wineberg, Yishay / Bar-Lev, Tali Hana / Futorian, Anna / Ben-Haim, Nissim / Armon, Leah / Ickowicz, Debby / Oriel, Sarit / Bucris, Efrat / Yehuda, Yishai / Pode-Shakked, Naomi / Gilad, Shlomit / Benjamin, Sima / Hohenstein, Peter / Dekel, Benjamin / Urbach, Achia / Kalisky, Tomer

    Journal of the American Society of Nephrology : JASN

    2020  Volume 31, Issue 10, Page(s) 2278–2291

    Abstract: Background: During mammalian kidney development, nephron progenitors undergo a mesenchymal-to-epithelial transition and eventually differentiate into the various tubular segments of the nephron. Recently, Drop-seq single-cell RNA sequencing technology ... ...

    Abstract Background: During mammalian kidney development, nephron progenitors undergo a mesenchymal-to-epithelial transition and eventually differentiate into the various tubular segments of the nephron. Recently, Drop-seq single-cell RNA sequencing technology for measuring gene expression from thousands of individual cells identified the different cell types in the developing kidney. However, that analysis did not include the additional layer of heterogeneity that alternative mRNA splicing creates.
    Methods: Full transcript length single-cell RNA sequencing characterized the transcriptomes of 544 individual cells from mouse embryonic kidneys.
    Results: Gene expression levels measured with full transcript length single-cell RNA sequencing identified each cell type. Further analysis comprehensively characterized splice isoform switching during the transition between mesenchymal and epithelial cellular states, which is a key transitional process in kidney development. The study also identified several putative splicing regulators, including the genes
    Conclusions: Discovery of the sets of genes that are alternatively spliced as the fetal kidney mesenchyme differentiates into tubular epithelium will improve our understanding of the molecular mechanisms that drive kidney development.
    MeSH term(s) Animals ; Cell Culture Techniques ; Kidney/embryology ; Mesoderm/embryology ; Mice ; Organogenesis/genetics ; RNA Isoforms ; Sequence Analysis, RNA ; Urothelium/embryology
    Chemical Substances RNA Isoforms
    Language English
    Publishing date 2020-07-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1085942-1
    ISSN 1533-3450 ; 1046-6673
    ISSN (online) 1533-3450
    ISSN 1046-6673
    DOI 10.1681/ASN.2019080770
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A brief review of single-cell transcriptomic technologies.

    Kalisky, Tomer / Oriel, Sarit / Bar-Lev, Tali Hana / Ben-Haim, Nissim / Trink, Ariel / Wineberg, Yishay / Kanter, Itamar / Gilad, Shlomit / Pyne, Saumyadipta

    Briefings in functional genomics

    2017  Volume 17, Issue 1, Page(s) 64–76

    Abstract: In recent years, there has been an effort to develop new technologies for measuring gene expression and sequence information from thousands of individual cells. Large data sets that were obtained using these 'single cell' technologies have allowed ... ...

    Abstract In recent years, there has been an effort to develop new technologies for measuring gene expression and sequence information from thousands of individual cells. Large data sets that were obtained using these 'single cell' technologies have allowed scientists to address fundamental questions in biomedicine ranging from stems cells and development to cancer and immunology. Here, we provide a brief review of recent developments in single-cell technology. Our intention is to provide a quick background for newcomers to the field as well as a deeper description of some of the leading technologies to date.
    MeSH term(s) Data Analysis ; Humans ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis/methods ; Transcriptome/genetics
    Chemical Substances RNA, Messenger
    Language English
    Publishing date 2017-10-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2540916-5
    ISSN 2041-2657 ; 2041-2649 ; 2041-2647
    ISSN (online) 2041-2657
    ISSN 2041-2649 ; 2041-2647
    DOI 10.1093/bfgp/elx019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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