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      Life of Pi: Exploring functions of Pi16+ fibroblasts

      review-article
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      F1000Research
      F1000 Research Limited
      fibroblast, Pi16

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          Abstract

          Fibroblasts are mesenchymal cells that are responsible for creating and maintaining tissue architecture through the production of extracellular matrix. These cells also play critical roles in processes such as wound repair and immune modulation in normal tissues and various disease states including fibrosis, autoimmunity, and cancer. Fibroblasts have a complex repertoire of functions that vary by organ, inflammatory state, and the developmental stage of an organism. How fibroblasts manage so many functions in such a context-dependent manner represents a gap in our understanding of these cells. One possibility is that a tissue-resident precursor cell state exists that provides the fibroblast lineage with flexibility during growth, inflammation, or other contexts that require dynamic tissue changes. Recent work has suggested that a precursor fibroblast cell state is marked by expression of Peptidase inhibitor 16 ( Pi16). This review aims to concatenate and compare studies on fibroblasts that express Pi16 to clarify the roles of this cell state in fibroblast lineage development and other functions.

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          Most cited references40

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          Cross-tissue organization of the fibroblast lineage

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            Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.

            Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence of at least two fibroblast lineages in murine dorsal skin. Lineage tracing and transplantation assays demonstrate that a single fibroblast lineage is responsible for the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation. Lineage-specific cell ablation leads to diminished connective tissue deposition in wounds and reduces melanoma growth. Using flow cytometry, we identify CD26/DPP4 as a surface marker that allows isolation of this lineage. Small molecule-based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. Identification and isolation of these lineages hold promise for translational medicine aimed at in vivo modulation of fibrogenic behavior.
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              Characterization of the adipocyte cellular lineage in vivo

              Mature adipocytes are generated through the proliferation and differentiation of precursor cells. Our prior studies identified adipocyte progenitors in white adipose tissue (WAT) as Lin−:CD29+:CD34+:Sca-1+:CD24+ (CD24+) cells that are capable of generating functional WAT 1 . Here, we employ several Cre recombinase mouse models to identify the adipocyte cellular lineage in vivo. While it has been proposed that white adipocytes are derived from endothelial 2 and hematopoietic 3, 4 lineages, we find that neither of these lineages label white adipocytes. However, platelet-derived growth factor receptor α (PdgfRα)-Cre trace labels all white adipocytes. Analysis of WAT from PdgfRα-Cre reporter mice identifies CD24+ and Lin−:CD29+:CD34+:Sca-1+:CD24− (CD24−) cells as adipocyte precursors. We show that CD24+ cells generate the CD24− population in vivo and the CD24− cells express late markers of adipogenesis. From these data we propose a model where the CD24+ adipocyte progenitors become further committed to the adipocyte lineage as CD24 expression is lost, generating CD24− preadipocytes. This characterization of the adipocyte cellular lineage will facilitate study of the mechanisms that regulate WAT formation in vivo and WAT mass expansion in obesity.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: VisualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Funding AcquisitionRole: SupervisionRole: VisualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000 Research Limited (London, UK )
                2046-1402
                20 February 2024
                2024
                : 13
                : 126
                Affiliations
                [1 ]Department of Immunology, University of Toronto, Toronto, Ontario, M5S1A8, Canada
                [1 ]Precision Research Center for Refractory Diseases, Shanghai General Hospital (Ringgold ID: 12482), Shanghai, Shanghai, China
                [1 ]Medical Research Center, Kantonsspital St.Gallen, St.Gallen, Switzerland
                Author notes

                No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0003-1902-622X
                https://orcid.org/0000-0003-1902-622X
                Article
                10.12688/f1000research.143511.1
                11196929
                38919948
                68f4e3f2-732c-4788-ab88-f3222768288e
                Copyright: © 2024 McCartney EE et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 February 2024
                Funding
                Funded by: Canadian Institutes of Health Research
                Award ID: 471606
                This work was funded by the Canadian Institutes of Health Research (471606).
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                Review
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                fibroblast,pi16
                fibroblast, pi16

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