A single type of progenitor cell maintains normal epidermis

According to the current model of adult epidermal homeostasis, skin tissue is maintained by two discrete populations of progenitor cells: self-renewing stem cells; and their progeny, known as transit amplifying cells, which differentiate after several rounds of cell division. By making use of inducible genetic labelling, we have tracked the fate of a representative sample of progenitor cells in mouse tail epidermis at single-cell resolution in vivo at time intervals up to one year. Here we show that clone-size distributions are consistent with a new model of homeostasis involving only one type of progenitor cell. These cells are found to undergo both symmetric and asymmetric division at rates that ensure epidermal homeostasis. The results raise important questions about the potential role of stem cells on tissue maintenance in vivo.

[1]  E. Fuchs,et al.  Defining the Epithelial Stem Cell Niche in Skin , 2004, Science.

[2]  Y. Barrandon,et al.  The multifaceted adult epidermal stem cell. , 2003, Current opinion in cell biology.

[3]  L. Taichman,et al.  Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin , 2001, The EMBO journal.

[4]  C. Potten Cell replacement in epidermis (keratopoiesis) via discrete units of proliferation. , 1981, International review of cytology.

[5]  John P. Sundberg,et al.  Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in wholemounts of mouse epidermis , 2003, Development.

[6]  B. Rannala,et al.  A stop‐EGFP transgenic mouse to detect clonal cell lineages generated by mutation , 2004, EMBO reports.

[7]  Yaping Liu,et al.  Capturing and profiling adult hair follicle stem cells , 2004, Nature Biotechnology.

[8]  I. Smart VARIATION IN THE PLANE OF CELL CLEAVAGE DURING THE PROCESS OF STRATIFICATION IN THE MOUSE EPIDERMIS , 1970, The British journal of dermatology.

[9]  William A. Harris,et al.  In Vivo Time-Lapse Imaging of Cell Divisions during Neurogenesis in the Developing Zebrafish Retina , 2003, Neuron.

[10]  Potten Cs Cell Replacement in Epidermis (Keratopoiesis) via Discrete Units of Proliferation , 1981 .

[11]  B. Rannala,et al.  Evidence from the stop‐EGFP mouse supports a niche‐sharing model of epidermal proliferative units , 2005, Experimental dermatology.

[12]  F. Watt,et al.  Epidermal label-retaining cells: background and recent applications. , 2004, The journal of investigative dermatology. Symposium proceedings.

[13]  H. Budka,et al.  Immunohistochemical detection of cell growth fraction in formalin-fixed and paraffin-embedded murine tissue. , 2001, The American journal of pathology.

[14]  B. Morgan,et al.  Distinct stem cell populations regenerate the follicle and interfollicular epidermis. , 2005, Developmental cell.

[15]  Richard Kemp,et al.  Elimination of background recombination: somatic induction of Cre by combined transcriptional regulation and hormone binding affinity. , 2004, Nucleic acids research.

[16]  L. Lajtha Stem cell concepts. , 1979, Nouvelle revue francaise d'hematologie.

[17]  M. Gho,et al.  Frizzled signalling controls orientation of asymmetric sense organ precursor cell divisions in Drosophila , 1998, Nature.

[18]  C. Potten THE EPIDERMAL PROLIFERATIVE UNIT: THE POSSIBLE ROLE OF THE CENTRAL BASAL CELL , 1974, Cell and tissue kinetics.

[19]  Yann Barrandon,et al.  Long-term renewal of hair follicles from clonogenic multipotent stem cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Raff,et al.  Clonal analysis of oligodendrocyte development in culture: Evidence for a developmental clock that counts cell divisions , 1986, Cell.

[21]  Masanobu Taniguchi,et al.  Elements of Stochastic Processes , 2000 .

[22]  Shankar Srinivas,et al.  Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus , 2001, BMC Developmental Biology.

[23]  A. Venkitaraman,et al.  Inhibition of Interleukin 7 Receptor Signaling by Antigen Receptor Assembly , 2000, The Journal of experimental medicine.

[24]  Y. Jan,et al.  Asymmetric Localization of a Mammalian Numb Homolog during Mouse Cortical Neurogenesis , 1996, Neuron.

[25]  I. Mackenzie Relationship between Mitosis and the Ordered Structure of the Stratum Corneum in Mouse Epidermis , 1970, Nature.

[26]  Elaine Fuchs,et al.  Asymmetric cell divisions promote stratification and differentiation of mammalian skin , 2005, Nature.

[27]  T. Rando,et al.  The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis. , 2002, Developmental cell.

[28]  Elaine Fuchs,et al.  Stem cells of the skin epithelium , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[29]  노원상 Evidence from the stop-EGFP mouse supports a niche-sharing model of epidermal proliferative units , 2005 .

[30]  G. Williams,et al.  Improved cervical smear assessment using antibodies against proteins that regulate DNA replication. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[31]  T. Mizutani,et al.  Analysis of the cellular heterogeneity in the basal layer of mouse ear epidermis: an approach from partial decomposition in vitro and retroviral cell marking in vivo. , 2003, Experimental cell research.