Article

Identification and prospective isolation of a mesothelial precursor lineage giving rise to smooth muscle cells and fibroblasts for mammalian internal organs, and their vasculature

Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature Cell Biology (Impact Factor: 19.68). 11/2012; 14(12). DOI: 10.1038/ncb2610
Source: PubMed

ABSTRACT

Fibroblasts and smooth muscle cells (FSMCs) are principal cell types of connective and adventitial tissues that participate in the development, physiology and pathology of internal organs, with incompletely defined cellular origins. Here, we identify and prospectively isolate from the mesothelium a mouse cell lineage that is committed to FSMCs. The mesothelium is an epithelial monolayer covering the vertebrate thoracic and abdominal cavities and internal organs. Time-lapse imaging and transplantation experiments reveal robust generation of FSMCs from the mesothelium. By targeting mesothelin (MSLN), a surface marker expressed on mesothelial cells, we identify and isolate precursors capable of clonally generating FSMCs. Using a genetic lineage tracing approach, we show that embryonic and adult mesothelium represents a common lineage to trunk FSMCs, and trunk vasculature, with minimal contributions from neural crest, or circulating cells. The isolation of FSMC precursors enables the examination of multiple aspects of smooth muscle and fibroblast biology as well as the prospective isolation of these precursors for potential regenerative medicine purposes.

2 Followers
 · 
15 Reads
  • Source
    • "However, for many organs (heart, lungs, liver, gut), Wt1-Cre is a good option for genetic lineage tracing of the CEDC (Wilm et al., 2005; Que et al., 2008; del Monte et al., 2011; Wessels et al., 2012; Carmona et al., 2013; Cano et al., 2013a). Mesothelin-Cre has recently been used for the tracing of the CEDC in the trunk, showing a wide contribution of these cells to the fibroblasts and smooth muscle of the trunk, as described below (Rinkevich et al., 2012). Our laboratory has recently used a Cre driver based on the G2- enhancer of the Gata4 gene (Rojas et al., 2005; Delgado et al., 2014). "

    Full-text · Dataset · Jan 2016
  • Source
    • "However, for many organs (heart, lungs, liver, gut), Wt1-Cre is a good option for genetic lineage tracing of the CEDC (Wilm et al., 2005; Que et al., 2008; del Monte et al., 2011; Wessels et al., 2012; Carmona et al., 2013; Cano et al., 2013a). Mesothelin-Cre has recently been used for the tracing of the CEDC in the trunk, showing a wide contribution of these cells to the fibroblasts and smooth muscle of the trunk, as described below (Rinkevich et al., 2012). Our laboratory has recently used a Cre driver based on the G2- enhancer of the Gata4 gene (Rojas et al., 2005; Delgado et al., 2014). "

    Full-text · Dataset · Jan 2016
  • Source
    • "These results of renal tubule-restricted clonal segment-specific epithelial cells are complemented by our previous studies that demonstrated generation of nonepithelial fibroblasts and smooth muscle cells from a mesothelial precursor lineage (Rinkevich et al., 2012) and collectively demonstrate a mechanism of organ renewal by tissue-and lineage-restricted precursors for both renal tubule and nontubule (endothelial, smooth muscle , mesothelium, and fibroblast) components. Like our studies on digit-tip regeneration in mice, wherein lineage-restricted local tissue-type-specific stem/progenitor cells (Rinkevich et al., 2012) rather than dedifferentiated pluripotent blastema cells are responsible for regeneration, and our previous studies that blood-forming stem cells can only make blood (Wagers et al., 2002), and not other tissues such as heart cells (Balsam et al., 2004), brain cells (Massengale et al., 2005), or any endoderm-derived epithelial cells (Wagers and Weissman, 2004) by transdifferentiation, it appears that the mouse and human body plans for tissue maintenance occurs via tissue-restricted and tissue subregion-specific cells with stem/progenitor characteristics. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The mechanism and magnitude by which the mammalian kidney generates and maintains its proximal tubules, distal tubules, and collecting ducts remain controversial. Here, we use long-term in vivo genetic lineage tracing and clonal analysis of individual cells from kidneys undergoing development, maintenance, and regeneration. We show that the adult mammalian kidney undergoes continuous tubulogenesis via expansions of fate-restricted clones. Kidneys recovering from damage undergo tubulogenesis through expansions of clones with segment-specific borders, and renal spheres developing in vitro from individual cells maintain distinct, segment-specific fates. Analysis of mice derived by transfer of color-marked embryonic stem cells (ESCs) into uncolored blastocysts demonstrates that nephrons are polyclonal, developing from expansions of singly fated clones. Finally, we show that adult renal clones are derived from Wnt-responsive precursors, and their tracing in vivo generates tubules that are segment specific. Collectively, these analyses demonstrate that fate-restricted precursors functioning as unipotent progenitors continuously maintain and self-preserve the mouse kidney throughout life.
    Full-text · Article · May 2014 · Cell Reports
Show more