CD133 Is a Marker for Long-Term Repopulating Murine Epidermal Stem Cells

Abstract

Maintenance, repair and renewal of the epidermis are thought to depend on a pool of dedicated epidermal stem cells. Like for many somatic tissues, isolation of a nearly pure population of stem cells is a primary goal in cutaneous biology. We used a quantitative transplantation assay, using injection of keratinocytes into subcutis combined with limiting dilution analysis, to assess the long-term repopulating ability of putative murine epidermal stem populations. Putative epidermal stem cell populations were isolated by FACS sorting. The CD133 + population and the subpopulation of CD133 + cells that exhibits high mitochondrial membrane potential (DΨm hi ) , were enriched for long-term repopulating epidermal stem cells vs. unfractionated cells (3.9 and 5.2-fold, respectively). Evidence for self-renewal capacity was obtained by serial transplantation of long-term epidermal repopulating units derived from CD133 + and CD133 + ΔΨm hi keratinocytes. CD133 + keratinocytes were multipotent and produced significantly more hair follicles than CD133 − cells. CD133 + cells were a subset of the previously described integrin α6 + CD34 + bulge cell population and 28.9±8.6% were label retaining cells. Thus, murine keratinocytes within the CD133 + and CD133 + ΔΨm hi populations contain epidermal stem cells that regenerate epidermis for the long-term, are self-renewing, multipotent, and label-retaining cells.

Pharmacological Mobilization of Endogenous Stem Cells Significantly Promotes Skin Regeneration after Full-Thickness Excision: The Synergistic Activity of AMD3100 and Tacrolimus

“…In this mouse model, progenitor CD133 cells were lacZ positive whereas the CD133 progeny were GFP positive. LacZ and GFP positive cells were observed only in the hair follicles of intact mouse skins (Figure 6b) as reported by others (Charruyer et al , 2012). …”

“…Lineage analysis has also demonstrated that follicles can arise from cells outside of the hair follicle stem cell niche, suggesting that cells found in the epidermis can assume a hair follicle stem cell phenotype (Ito et al , 2007). A recent study reported that CD133 is a marker for long-term repopulating murine epidermal stem cells and CD133+ keratinocytes formed both hair follicles and epidermis after injection into immunodeficient mice (Charruyer et al , 2012). Our lineage tracing studies demonstrated the presence of CD133+ cells in the hair follicles of intact skin (Figure 6b).…”

Mitochondrial-Targeted Decyl-Triphenylphosphonium Enhances 2-Deoxy-D-Glucose Mediated Oxidative Stress and Clonogenic Killing of Multiple Myeloma Cells

“…Recent reports showing that normal stem cells and induced pluripotent stem cells retain young mitochondria with high metabolic capacity [54, 110, 111]. Similarly, physiological aging may occur in cancer where CSCs show hyperpolarized Δψ m [24, 44, 45].…”

CD133 in the Selection of Epidermal Stem Cells in Mice: Steps in the Right Direction

“…Consequently, the Ghadially group (Charruyer et al, 2012) achieved a 5.2-fold enrichment with CD133 þ DCm hi keratinocytes over the a6 þ CD34 þ controls. Moreover, this enriched subpopulation displayed superior long-term repopulating and self-renewal abilities; it was composed of label-retaining cells, but retained the ability to reconstitute an epithelium with the epidermis, hair follicles, and sebaceous glands.…”

“…Furthermore, keratinocyte stem cells have long been implicated as target cells for non-melanoma skin cancer (Owens and Watt, 2003), and the identification of CD133 in a subset of normal hair follicle bulge stem cells, as shown by Ghadially and co-workers (Charruyer et al, 2012), may have important implications for skin tumorigenesis. Although CD133 is a transmembrane protein of unknown function, as neither ligands nor signaling pathways have been found to associate with it, multiple lines of evidence indicate that the presence of CD133 on the cell surface may serve as a functionally relevant biomarker for carcinogenesis.…”