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Tudorita Tumbar,Geraldine Guasch,Valentina Greco,Cedric Blanpain,William E. Lowry,Michael Rendl,Elaine Fuchs*
Many adult regenerative cells divide infrequently but have highproliferative capacity. We developed a strategy to fluorescentlylabel slow-cycling cells in a cell typespecific fashion.We used this method to purify the label-retaining cells (LRCs)that mark the skin stem cell (SC) niche. We found that thesecells rarely divide within their niche but change propertiesabruptly when stimulated to exit. We determined their transcriptionalprofile, which, when compared to progeny and other SCs, definesthe niche. Many of the >100 messenger RNAs preferentiallyexpressed in the niche encode surface receptors and secretedproteins, enabling LRCs to signal and respond to their environment.
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, Rockefeller University, New York, NY 10021, USA.
* To whom correspondence should be addressed. E-mail: fuchslb{at}rockefeller.edu
Wnt signaling promotes proliferation and stemness regulation of spermatogonial stem/progenitor cells.
N. Golestaneh, E. Beauchamp, S. Fallen, M. Kokkinaki, A. Uren, and M. Dym (2009)
Reproduction
138, 151-162
|Abstract »|Full Text »|PDF »
Change in gene expression of mouse embryonic stem cells derived from parthenogenetic activation.
S. P. Gong, H. Kim, E. J. Lee, S. T. Lee, S. Moon, H.-J. Lee, and J. M. Lim (2009)
Hum. Reprod.
24, 805-814
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The Molecular Regulation of Muscle Stem Cell Function.
M.A. Rudnicki, F. Le Grand, I. McKinnell, and S. Kuang (2009)
Cold Spring Harb Symp Quant Biol
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Corneal Limbal Microenvironment Can Induce Transdifferentiation of Hair Follicle Stem Cells into Corneal Epithelial-like Cells.
E. A. Blazejewska, U. Schlotzer-Schrehardt, M. Zenkel, B. Bachmann, E. Chankiewitz, C. Jacobi, and F. E. Kruse (2009)
Stem Cells
27, 642-652
|Abstract »|Full Text »|PDF »
Wnt Signaling, Lgr5, and Stem Cells in the Intestine and Skin.
Cancer Stem Cells Are Enriched in the Side Population Cells in a Mouse Model of Glioma.
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68, 10051-10059
|Abstract »|Full Text »|PDF »
Stem Cells, Their Niches and the Systemic Environment: An Aging Network.
Stem Cell Biology in the Lung and Lung Cancers: Employing Pulmonary Context and Classic Approaches.
D.M. Raiser, S.J. Zacharek, R.R. Roach, S.J. Curtis, K.W. Sinkevicius, D.W. Gludish, and C.F. Kim (2008)
Cold Spring Harb Symp Quant Biol
|Abstract »|PDF »
Very Long-term Self-renewal of Small Intestine, Colon, and Hair Follicles from Cycling Lgr5+ve Stem Cells.
N. Barker, J.H. van Es, V. Jaks, M. Kasper, H. Snippert, R. Toftgard, and H. Clevers (2008)
Cold Spring Harb Symp Quant Biol
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Building Epithelial Tissues from Skin Stem Cells.
E. Fuchs and J.A. Nowak (2008)
Cold Spring Harb Symp Quant Biol
|Abstract »|PDF »
The Majority of Multipotent Epidermal Stem Cells Do Not Protect Their Genome by Asymmetrical Chromosome Segregation.
P. A. Sotiropoulou, A. Candi, and C. Blanpain (2008)
Stem Cells
26, 2964-2973
|Abstract »|Full Text »|PDF »
White Fat Progenitor Cells Reside in the Adipose Vasculature.
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Science
322, 583-586
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Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics.
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PNAS
105, 12469-12473
|Abstract »|Full Text »|PDF »
Diverse Adult Stem Cells Share Specific Higher-Order Patterns of Gene Expression.
J. M. Doherty, M. J. Geske, T. S. Stappenbeck, and J. C. Mills (2008)
Stem Cells
26, 2124-2130
|Abstract »|Full Text »|PDF »
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Genes & Dev.
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One more reason to save your hair.
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Cardiovasc Res
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Cardiovasc Res
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|Abstract »|Full Text »|PDF »
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Am J Physiol Renal Physiol
294, F1415-F1421
|Abstract »|Full Text »|PDF »
Limbal Epithelial Crypt: A Model for Corneal Epithelial Maintenance and Novel Limbal Regional Variations.
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Arch Ophthalmol
126, 665-669
|Abstract »|Full Text »|PDF »
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D. Larouche, X. Tong, J. Fradette, P. A. Coulombe, and L. Germain (2008)
FASEB J
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Comparative Analysis of the Frequency and Distribution of Stem and Progenitor Cells in the Adult Mouse Brain.
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Stem Cells
26, 979-987
|Abstract »|Full Text »|PDF »
Runx1 modulates developmental, but not injury-driven, hair follicle stem cell activation.
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Development
135, 1059-1068
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Activation of Cardiac Progenitor Cells Reverses the Failing Heart Senescent Phenotype and Prolongs Lifespan.
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|Abstract »|Full Text »|PDF »
Progenitor/stem cells give rise to liver cancer due to aberrant TGF-{beta} and IL-6 signaling.
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PNAS
105, 2445-2450
|Abstract »|Full Text »|PDF »
BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties.
Multipotent skin-derived precursors: adult neural crest-related precursors with therapeutic potential.
K. J.L Fernandes, J. G Toma, and F. D Miller (2008)
Phil Trans R Soc B
363, 185-198
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The hematopoietic stem cell and its niche: a comparative view.
J. A. Martinez-Agosto, H. K.A. Mikkola, V. Hartenstein, and U. Banerjee (2007)
Genes & Dev.
21, 3044-3060
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Malignant astrocytic glioma: genetics, biology, and paths to treatment.
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Paving the road for lung stem cell biology: bronchioalveolar stem cells and other putative distal lung stem cells.
Self-Renewal and Multilineage Differentiation In Vitro from Murine Prostate Stem Cells.
L. Xin, R. U. Lukacs, D. A. Lawson, D. Cheng, and O. N. Witte (2007)
Stem Cells
25, 2760-2769
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Dual Role of {alpha}6beta4 Integrin in Epidermal Tumor Growth: Tumor-suppressive Versus Tumor-promoting Function.
K. Raymond, M. Kreft, J.-Y. Song, H. Janssen, and A. Sonnenberg (2007)
Mol. Biol. Cell
18, 4210-4221
|Abstract »|Full Text »|PDF »
Telomerase reverses epidermal hair follicle stem cell defects and loss of long-term survival associated with critically short telomeres.
I. Siegl-Cachedenier, I. Flores, P. Klatt, and M. A. Blasco (2007)
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179, 277-290
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Transforming Growth Factor-{beta} Can Suppress Tumorigenesis through Effects on the Putative Cancer Stem or Early Progenitor Cell and Committed Progeny in a Breast Cancer Xenograft Model.
B. Tang, N. Yoo, M. Vu, M. Mamura, J.-S. Nam, A. Ooshima, Z. Du, P.-Y. Desprez, M. R. Anver, A. M. Michalowska, et al. (2007)
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Am J Physiol Cell Physiol
293, C1082-C1092
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Syntenin mediates Delta1-induced cohesiveness of epidermal stem cells in culture.
Augmented Wnt Signaling in a Mammalian Model of Accelerated Aging.
H. Liu, M. M Fergusson, R. M. Castilho, J. Liu, L. Cao, J. Chen, D. Malide, I. I. Rovira, D. Schimel, C. J. Kuo, et al. (2007)
Science
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PNAS
104, 13040-13045
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C/EBP{delta} regulates cell cycle and self-renewal of human limbal stem cells.
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177, 1037-1049
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Isolation of a mesenchymal cell population from murine dermis that contains progenitors of multiple cell lineages.
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FASEB J
21, 2050-2063
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Bmi-1-Green Fluorescent Protein-Knock-In Mice Reveal the Dynamic Regulation of Bmi-1 Expression in Normal and Leukemic Hematopoietic Cells.
N. Hosen, T. Yamane, M. Muijtjens, K. Pham, M. F. Clarke, and I. L. Weissman (2007)
Stem Cells
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PNAS
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PNAS
104, 9428-9433
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CD34 Expression by Hair Follicle Stem Cells Is Required for Skin Tumor Development in Mice.
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67, 4173-4181
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Epidermal stem cells arise from the hair follicle after wounding.
V. Levy, C. Lindon, Y. Zheng, B. D. Harfe, and B. A. Morgan (2007)
FASEB J
21, 1358-1366
|Abstract »|Full Text »|PDF »
Stem/Progenitor Cell-Like Properties of Desmoglein 3dim Cells in Primary and Immortalized Keratinocyte Lines.
H. Wan, M. Yuan, C. Simpson, K. Allen, F. N.E. Gavins, M. S. Ikram, S. Basu, N. Baksh, E. A. O'Toole, and I. R. Hart (2007)
Stem Cells
25, 1286-1297
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Adult Mouse Myometrial Label-Retaining Cells Divide in Response to Gonadotropin Stimulation.
P. P. Szotek, H. L. Chang, L. Zhang, F. Preffer, D. Dombkowski, P. K. Donahoe, and J. Teixeira (2007)
Stem Cells
25, 1317-1325
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M. Tscharntke, R. Pofahl, A. Chrostek-Grashoff, N. Smyth, C. Niessen, C. Niemann, B. Hartwig, V. Herzog, H. W. Klein, T. Krieg, et al. (2007)
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120, 1480-1490
|Abstract »|Full Text »|PDF »
Evidence for a stem cell hierarchy in the adult human breast.
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J. Cell Biol.
177, 87-101
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J. A. Jeong, K.-M. Ko, S. Bae, C.-J. Jeon, G. Young Koh, and H. Kim (2007)
Stem Cells
25, 994-1002
|Abstract »|Full Text »|PDF »
Notch signaling controls germline stem cell niche formation in the Drosophila ovary.
X. Song, G. B. Call, D. Kirilly, and T. Xie (2007)
Development
134, 1071-1080
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Identification of Human Oral Keratinocyte Stem/Progenitor Cells by Neurotrophin Receptor p75 and the Role of Neurotrophin/p75 Signaling.
Lipid defect underlies selective skin barrier impairment of an epidermal-specific deletion of Gata-3.
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J. Cell Biol.
175, 661-670
|Abstract »|Full Text »|PDF »
Concise Review: Recent Advances on the Significance of Stem Cells in Tissue Regeneration and Cancer Therapies.
A Role for Angiotensin-Converting Enzyme in the Characterization, Enrichment, and Proliferation Potential of Adult Murine Pituitary Colony-Forming Cells.
D. A. Lepore, V. J. Jokubaitis, P. J. Simmons, K. N. Roeszler, R. Rossi, K. Bauer, and P. Q. Thomas (2006)
Stem Cells
24, 2382-2390
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Repression of Nanog Gene Transcription by Tcf3 Limits Embryonic Stem Cell Self-Renewal.
L. Pereira, F. Yi, and B. J. Merrill (2006)
Mol. Cell. Biol.
26, 7479-7491
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Regulation of epidermal homeostasis and repair by phosphoinositide 3-kinase.
S. Pankow, C. Bamberger, A. Klippel, and S. Werner (2006)
J. Cell Sci.
119, 4033-4046
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Global Transcriptome Analysis of Genetically Identified Neurons in the Adult Cortex.
M. J. Rossner, J. Hirrlinger, S. P. Wichert, C. Boehm, D. Newrzella, H. Hiemisch, G. Eisenhardt, C. Stuenkel, O. von Ahsen, and K.-A. Nave (2006)
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26, 9956-9966
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Epidermal and craniofacial defects in mice overexpressing Klf5 in the basal layer of the epidermis.
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119, 3593-3601
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Side population in adult murine epidermis exhibits phenotypic and functional characteristics of keratinocyte stem cells.
Restricted epithelial proliferation by lacritin via PKC{alpha}-dependent NFAT and mTOR pathways.
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174, 689-700
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Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence.
Selective Modulation of Hedgehog/GLI Target Gene Expression by Epidermal Growth Factor Signaling in Human Keratinocytes..
M. Kasper, H. Schnidar, G. W. Neill, M. Hanneder, S. Klingler, L. Blaas, C. Schmid, C. Hauser-Kronberger, G. Regl, M. P. Philpott, et al. (2006)
Mol. Cell. Biol.
26, 6283-6298
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Proximal Prostatic Stem Cells Are Programmed to Regenerate a Proximal-Distal Ductal Axis.
K. Goto, S. N. Salm, S. Coetzee, X. Xiong, P. E. Burger, E. Shapiro, H. Lepor, D. Moscatelli, and E. L. Wilson (2006)
Stem Cells
24, 1859-1868
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The cell-surface marker MTS24 identifies a novel population of follicular keratinocytes with characteristics of progenitor cells.
J. G. W. Nijhof, K. M. Braun, A. Giangreco, C. van Pelt, H. Kawamoto, R. L. Boyd, R. Willemze, L. H. F. Mullenders, F. M. Watt, F. R. de Gruijl, et al. (2006)
Development
133, 3027-3037
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Transcriptional Profiling of Enriched Populations of Stem Cells Versus Transient Amplifying Cells: A COMPARISON OF LIMBAL AND CORNEAL EPITHELIAL BASAL CELLS.
M. Zhou, X.-m. Li, and R. M. Lavker (2006)
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281, 19600-19609
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A hierarchy of proliferative cells exists in mouse lens epithelium: implications for lens maintenance..
M. Zhou, J. Leiberman, J. Xu, and R. M. Lavker (2006)
Invest. Ophthalmol. Vis. Sci.
47, 2997-3003
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Identification and Functional Analysis of Candidate Genes Regulating Mesenchymal Stem Cell Self-Renewal and Multipotency.
L. Song, N. E. Webb, Y. Song, and R. S. Tuan (2006)
Stem Cells
24, 1707-1718
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Epithelial stem cells of the lung: privileged few or opportunities for many?.