Stem Cells and Niches: Mechanisms That Promote Stem Cell Maintenance throughout Life

Niches are local tissue microenvironments that maintain and regulate stem cells. Long-predicted from mammalian studies, these structures have recently been characterized within several invertebrate tissues using methods that reliably identify individual stem cells and their functional requirements. Although similar single-cell resolution has usually not been achieved in mammalian tissues, principles likely to govern the behavior of niches in diverse organisms are emerging. Considerable progress has been made in elucidating how the microenvironment promotes stem cell maintenance. Mechanisms of stem cell maintenance are key to the regulation of homeostasis and likely contribute to aging and tumorigenesis when altered during adulthood.

[1]  E. Matunis,et al.  Regeneration of Male Germline Stem Cells by Spermatogonial Dedifferentiation in Vivo , 2004, Science.

[2]  T. Palmer,et al.  Vascular niche for adult hippocampal neurogenesis , 2000, The Journal of comparative neurology.

[3]  S. Nilsson,et al.  Spatial localization of transplanted hemopoietic stem cells: inferences for the localization of stem cell niches. , 2001, Blood.

[4]  Dana T Byrd,et al.  Cellular analyses of the mitotic region in the Caenorhabditis elegans adult germ line. , 2006, Molecular biology of the cell.

[5]  N. Perrimon,et al.  BMP signaling is required for controlling somatic stem cell self-renewal in the Drosophila ovary. , 2005, Developmental cell.

[6]  A. Joyner,et al.  In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog , 2005, Nature.

[7]  Shenghui He,et al.  Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU , 2007, Nature.

[8]  H. Macdonald,et al.  Simultaneous loss of β- and γ-catenin does not perturb hematopoiesis or lymphopoiesis , 2008 .

[9]  M. Götz,et al.  The cell biology of neurogenesis , 2006, International Journal of Developmental Neuroscience.

[10]  T. Nagasawa,et al.  Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. , 2006, Immunity.

[11]  L. Parada,et al.  Nf1+/- mast cells induce neurofibroma like phenotypes through secreted TGF-beta signaling. , 2006, Human molecular genetics.

[12]  P. Gönczy,et al.  bag-of-marbles and benign gonial cell neoplasm act in the germline to restrict proliferation during Drosophila spermatogenesis. , 1997, Development.

[13]  David J. Anderson,et al.  Deregulation of Dorsoventral Patterning by FGF Confers Trilineage Differentiation Capacity on CNS Stem Cells In Vitro , 2003, Neuron.

[14]  A. Spradling,et al.  Differentiating germ cells can revert into functional stem cells in Drosophila melanogaster ovaries , 2004, Nature.

[15]  I. Weissman,et al.  Identification of a lineage of multipotent hematopoietic progenitors. , 1997, Development.

[16]  A. Petrie,et al.  Stem Cell Function, Self-Renewal, and Behavioral Heterogeneity of Cells from the Adult Muscle Satellite Cell Niche , 2005, Cell.

[17]  A. Fernández-Miñan,et al.  Jak/Stat signalling in niche support cells regulates dpp transcription to control germline stem cell maintenance in the Drosophila ovary , 2008, Development.

[18]  Tak W. Mak,et al.  Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells , 2004, Nature.

[19]  Ting Xie,et al.  Germline Stem Cells Anchored by Adherens Junctions in the Drosophila Ovary Niches , 2002, Science.

[20]  A. Spradling,et al.  Multipotent Drosophila Intestinal Stem Cells Specify Daughter Cell Fates by Differential Notch Signaling , 2007, Science.

[21]  Chris Q Doe,et al.  Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe , 2007, Neural Development.

[22]  Y. Nabeshima,et al.  Stem Cell Heterogeneity , 2007, Annals of the New York Academy of Sciences.

[23]  R. Lehmann,et al.  Soma–germline interactions coordinate homeostasis and growth in the Drosophila gonad , 2006, Nature.

[24]  P. Ingham,et al.  hedgehog is required for the proliferation and specification of ovarian somatic cells prior to egg chamber formation in Drosophila. , 1996, Development.

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

[26]  高野 弥奈 Asymmetric division and lineage commitment at the level of hematopoietic stem cells : inference from differentiation in daughter cell and granddaughter cell pairs , 2004 .

[27]  S. Morrison,et al.  Supplemental Experimental Procedures , 2022 .

[28]  A. Spradling,et al.  An epithelial niche in the Drosophila ovary undergoes long-range stem cell replacement. , 2007, Cell stem cell.

[29]  W. Deng,et al.  Spectrosomes and fusomes anchor mitotic spindles during asymmetric germ cell divisions and facilitate the formation of a polarized microtubule array for oocyte specification in Drosophila. , 1997, Developmental biology.

[30]  Renuka R. Nayak,et al.  Dynamics of the male germline stem cell population during aging of Drosophila melanogaster , 2006, Aging cell.

[31]  Fred H. Gage,et al.  The Adult Rat Hippocampus Contains Primordial Neural Stem Cells , 1997, Molecular and Cellular Neuroscience.

[32]  A. Spradling,et al.  Stem cells and their progeny respond to nutritional changes during Drosophila oogenesis. , 2001, Developmental biology.

[33]  T. Xie,et al.  DE-cadherin-mediated cell adhesion is essential for maintaining somatic stem cells in the Drosophila ovary , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Elaine Fuchs,et al.  Self-Renewal, Multipotency, and the Existence of Two Cell Populations within an Epithelial Stem Cell Niche , 2004, Cell.

[35]  J. Dick,et al.  Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell , 1997, Nature Medicine.

[36]  Keisuke Ito,et al.  Tie2/Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche , 2004, Cell.

[37]  M. Rudnicki,et al.  Asymmetric Self-Renewal and Commitment of Satellite Stem Cells in Muscle , 2007, Cell.

[38]  D. D. de Rooij Proliferation and differentiation of spermatogonial stem cells. , 2001, Reproduction.

[39]  T. Rando The Immortal Strand Hypothesis: Segregation and Reconstruction , 2007, Cell.

[40]  David A. Williams,et al.  Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells. , 2003, The Journal of clinical investigation.

[41]  E. Fuchs,et al.  Loss of a quiescent niche but not follicle stem cells in the absence of bone morphogenetic protein signaling , 2007, Proceedings of the National Academy of Sciences.

[42]  Ting Xie,et al.  decapentaplegic Is Essential for the Maintenance and Division of Germline Stem Cells in the Drosophila Ovary , 1998, Cell.

[43]  A. Spradling,et al.  An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[44]  I. Weissman,et al.  Wnt proteins are lipid-modified and can act as stem cell growth factors , 2003, Nature.

[45]  Kristin J. Robinson,et al.  Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation , 2006, Nature.

[46]  Mayumi Ito,et al.  Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding , 2007, Nature.

[47]  A. Mahowald,et al.  Asymmetric Inheritance of Mother Versus Daughter Centrosome in Stem Cell Division , 2007, Science.

[48]  H. Clevers,et al.  Identification of stem cells in small intestine and colon by marker gene Lgr5 , 2007, Nature.

[49]  A. Spradling,et al.  The Drosophila ovarian and testis stem cell niches: similar somatic stem cells and signals. , 2005, Developmental cell.

[50]  E. Matunis,et al.  Control of Stem Cell Self-Renewal in Drosophila Spermatogenesis by JAK-STAT Signaling , 2001, Science.

[51]  Ting Xie,et al.  Differentiation-defective stem cells outcompete normal stem cells for niche occupancy in the Drosophila ovary. , 2008, Cell stem cell.

[52]  B. Sacchetti,et al.  Self-Renewing Osteoprogenitors in Bone Marrow Sinusoids Can Organize a Hematopoietic Microenvironment , 2007, Cell.

[53]  T. Sun,et al.  Label-retaining cells reside in the bulge area of pilosebaceous unit: Implications for follicular stem cells, hair cycle, and skin carcinogenesis , 1990, Cell.

[54]  H. Okano,et al.  Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells. , 2004, Immunity.

[55]  David J. Anderson,et al.  Prospective Identification, Isolation by Flow Cytometry, and In Vivo Self-Renewal of Multipotent Mammalian Neural Crest Stem Cells , 1999, Cell.

[56]  John Cairns,et al.  Mutation selection and the natural history of cancer , 1975, Nature.

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

[58]  Gina A. Taylor,et al.  Involvement of Follicular Stem Cells in Forming Not Only the Follicle but Also the Epidermis , 2000, Cell.

[59]  S. Redick,et al.  Centriolin Anchoring of Exocyst and SNARE Complexes at the Midbody Is Required for Secretory-Vesicle-Mediated Abscission , 2005, Cell.

[60]  L. Coussens,et al.  Tumor stroma and regulation of cancer development. , 2006, Annual review of pathology.

[61]  S. Morrison,et al.  Cell-Intrinsic Differences between Stem Cells from Different Regions of the Peripheral Nervous System Regulate the Generation of Neural Diversity , 2002, Neuron.

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

[63]  S. Orkin,et al.  Rb Regulates Interactions between Hematopoietic Stem Cells and Their Bone Marrow Microenvironment , 2007, Cell.

[64]  H. Macdonald,et al.  Simultaneous loss of beta- and gamma-catenin does not perturb hematopoiesis or lymphopoiesis. , 2008, Blood.

[65]  I. Weissman,et al.  A role for Wnt signalling in self-renewal of haematopoietic stem cells , 2003, Nature.

[66]  S. Morrison,et al.  Toward an understanding of the physiological function of Mammalian stem cells. , 2005, Developmental cell.

[67]  Arturo Alvarez-Buylla,et al.  Mosaic Organization of Neural Stem Cells in the Adult Brain , 2007, Science.

[68]  E. Brown,et al.  Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor , 2006, Nature.

[69]  T. Rando,et al.  Stem cells in postnatal myogenesis: molecular mechanisms of satellite cell quiescence, activation and replenishment. , 2005, Trends in cell biology.

[70]  Monica Boyle,et al.  Decline in self-renewal factors contributes to aging of the stem cell niche in the Drosophila testis. , 2007, Cell stem cell.

[71]  I. Weissman,et al.  Stem Cells Are Units of Natural Selection in a Colonial Ascidian , 2006, Cell.

[72]  L. Mahadevan,et al.  Vanadate stimulates differentiation and neurite outgrowth in rat pheochromocytoma PC12 cells and neurite extension in human neuroblastoma SH-SY5Y cells , 1994, Neuroscience.

[73]  D. Berdnik,et al.  Asymmetric Rab11 Endosomes Regulate Delta Recycling and Specify Cell Fate in the Drosophila Nervous System , 2005, Cell.

[74]  Benjamin D. Simons,et al.  A single type of progenitor cell maintains normal epidermis , 2007, Nature.

[75]  Michael F. Clarke,et al.  Applying the principles of stem-cell biology to cancer , 2003, Nature Reviews Cancer.

[76]  Ari Elson,et al.  Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells , 2006, Nature Medicine.

[77]  Gerald B Call,et al.  Notch signaling controls germline stem cell niche formation in the Drosophila ovary , 2007, Development.

[78]  M. Raff,et al.  Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells. , 2000, Science.

[79]  Daniel A. Lim,et al.  Subventricular Zone Astrocytes Are Neural Stem Cells in the Adult Mammalian Brain , 1999, Cell.

[80]  D. Burns,et al.  Neurofibromas in NF1: Schwann Cell Origin and Role of Tumor Environment , 2002, Science.

[81]  Irving L. Weissman,et al.  Physiological Migration of Hematopoietic Stem and Progenitor Cells , 2001, Science.

[82]  M. Loeffler,et al.  Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. , 1990, Development.

[83]  Sally Temple,et al.  Endothelial Cells Stimulate Self-Renewal and Expand Neurogenesis of Neural Stem Cells , 2004, Science.

[84]  Y. Nabeshima,et al.  A Vasculature-Associated Niche for Undifferentiated Spermatogonia in the Mouse Testis , 2007, Science.

[85]  A. Spradling,et al.  A niche maintaining germ line stem cells in the Drosophila ovary. , 2000, Science.

[86]  G. Fishell,et al.  Hedgehog Signaling in the Subventricular Zone Is Required for Both the Maintenance of Stem Cells and the Migration of Newborn Neurons , 2007, The Journal of Neuroscience.

[87]  F. Doetsch,et al.  A niche for adult neural stem cells. , 2003, Current opinion in genetics & development.

[88]  C. Doe,et al.  The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts , 2006, Nature Cell Biology.

[89]  J. Kimble,et al.  Controls of germline stem cells, entry into meiosis, and the sperm/oocyte decision in Caenorhabditis elegans. , 2007, Annual review of cell and developmental biology.

[90]  P. Chambon,et al.  A Microenvironment-Induced Myeloproliferative Syndrome Caused by Retinoic Acid Receptor γ Deficiency , 2007, Cell.

[91]  Elaine Fuchs,et al.  Epidermal stem cells of the skin. , 2006, Annual review of cell and developmental biology.

[92]  G. Sauvageau,et al.  Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells , 2003, Nature.

[93]  D. Scadden,et al.  Osteoblastic cells regulate the haematopoietic stem cell niche , 2003, Nature.

[94]  M. Blasco,et al.  Cellular Senescence in Cancer and Aging , 2007, Cell.

[95]  U. Suter,et al.  Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation. , 2005, Blood.

[96]  Gerald B Call,et al.  Stem cell aging is controlled both intrinsically and extrinsically in the Drosophila ovary. , 2007, Cell stem cell.

[97]  Ross Tubo,et al.  Mesenchymal stem cells within tumour stroma promote breast cancer metastasis , 2007, Nature.

[98]  M. Fuller,et al.  Orientation of Asymmetric Stem Cell Division by the APC Tumor Suppressor and Centrosome , 2003, Science.

[99]  A. Kiger,et al.  Stem Cell Self-Renewal Specified by JAK-STAT Activation in Response to a Support Cell Cue , 2001, Science.

[100]  N. Kessaris,et al.  Subventricular Zone Stem Cells Are Heterogeneous with Respect to Their Embryonic Origins and Neurogenic Fates in the Adult Olfactory Bulb , 2007, The Journal of Neuroscience.

[101]  Haiyang Huang,et al.  Identification of the haematopoietic stem cell niche and control of the niche size , 2003, Nature.

[102]  H. Ruohola-Baker,et al.  Stem Cells Signal to the Niche through the Notch Pathway in the Drosophila Ovary , 2006, Current Biology.

[103]  N. Perrimon,et al.  GFP reporters detect the activation of the Drosophila JAK/STAT pathway in vivo. , 2007, Gene expression patterns : GEP.

[104]  A. Spradling,et al.  Identification and behavior of epithelial stem cells in the Drosophila ovary. , 1995, Development.

[105]  Y. Nabeshima,et al.  Functional identification of the actual and potential stem cell compartments in mouse spermatogenesis. , 2007, Developmental cell.

[106]  A. Spradling,et al.  Male and Female Drosophila Germline Stem Cells: Two Versions of Immortality , 2007, Science.

[107]  D. Alling,et al.  Large numbers of primitive stem cells are active simultaneously in aggregated embryo chimeric mice. , 1987, Blood.

[108]  Sean J. Morrison,et al.  Asymmetric and symmetric stem-cell divisions in development and cancer , 2006, Nature.

[109]  T. Xie,et al.  wingless signaling regulates the maintenance of ovarian somatic stem cells in Drosophila , 2003, Development.

[110]  D. Scadden,et al.  The hematopoietic stem cell in its place , 2006, Nature Immunology.

[111]  S. Krauss,et al.  Continuing role for mouse Numb and Numbl in maintaining progenitor cells during cortical neurogenesis , 2004, Nature Neuroscience.

[112]  I. Weissman,et al.  Stem cells, cancer, and cancer stem cells , 2001, Nature.

[113]  I. Bayazitov,et al.  A perivascular niche for brain tumor stem cells. , 2007, Cancer cell.

[114]  T. Xie,et al.  Gbb/Bmp signaling is essential for maintaining germline stem cells and for repressing bam transcription in the Drosophila testis , 2004, Development.

[115]  R. Henkelman,et al.  Identification of human brain tumour initiating cells , 2004, Nature.

[116]  S. Morrison,et al.  Lack of evidence that hematopoietic stem cells depend on N-cadherin-mediated adhesion to osteoblasts for their maintenance. , 2007, Cell stem cell.

[117]  P. Ingham,et al.  Regulation of Stem Cell Maintenance and Transit Amplifying Cell Proliferation by TGF-β Signaling in Drosophila Spermatogenesis , 2003, Current Biology.