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      Identification, discrimination and heterogeneity of fibroblasts

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          Abstract

          Fibroblasts, the principal cell type of connective tissue, secrete extracellular matrix components during tissue development, homeostasis, repair and disease. Despite this crucial role, the identification and distinction of fibroblasts from other cell types are challenging and laden with caveats. Rapid progress in single-cell transcriptomics now yields detailed molecular portraits of fibroblasts and other cell types in our bodies, which complement and enrich classical histological and immunological descriptions, improve cell class definitions and guide further studies on the functional heterogeneity of cell subtypes and states, origins and fates in physiological and pathological processes. In this review, we summarize and discuss recent advances in the understanding of fibroblast identification and heterogeneity and how they discriminate from other cell types.

          Abstract

          In this review, the authors look at how recent progress in single-cell transcriptomics complement and enrich the classical, largely morphological, portraits of fibroblasts. The detailed molecular information now available provides new insights into fibroblast identity, heterogeneity and function.

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          Most cited references223

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          Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

          Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
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            Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

            The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
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              The basics of epithelial-mesenchymal transition.

              The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.
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                Author and article information

                Contributors
                christer.betsholtz@igp.uu.se
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                14 June 2022
                14 June 2022
                2022
                : 13
                : 3409
                Affiliations
                [1 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Department of Cell and Molecular Biology, , Karolinska Institutet, ; SE-171 77 Stockholm, Sweden
                [2 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Department of Neurobiology, , Care sciences and Society, Karolinska Institutet, ; SE-14183 Huddinge, Sweden
                [3 ]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Department of Medicine, , Huddinge, Karolinska Institutet, ; Blickagången 16, SE-141 57 Huddinge, Sweden
                [4 ]GRID grid.8993.b, ISNI 0000 0004 1936 9457, Department of Immunology, , Genetics and Pathology, Rudbeck Laboratory, Uppsala University, ; Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden
                Author information
                http://orcid.org/0000-0001-9543-8141
                http://orcid.org/0000-0003-0952-0507
                Article
                30633
                10.1038/s41467-022-30633-9
                9192344
                35701396
                478ed349-5703-4463-aa64-f4a554bd38d5
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 24 May 2021
                : 4 May 2022
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2022

                Uncategorized
                mechanisms of disease,cells
                Uncategorized
                mechanisms of disease, cells

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