Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2005-01-23

AUTHORS

Andrew W Duncan, Frédérique M Rattis, Leah N DiMascio, Kendra L Congdon, Gregory Pazianos, Chen Zhao, Keejung Yoon, J Michael Cook, Karl Willert, Nicholas Gaiano, Tannishtha Reya

ABSTRACT

A fundamental question in hematopoietic stem cell (HSC) biology is how self-renewal is controlled. Here we show that the molecular regulation of two critical elements of self-renewal, inhibition of differentiation and induction of proliferation, can be uncoupled, and we identify Notch signaling as a key factor in inhibiting differentiation. Using transgenic Notch reporter mice, we found that Notch signaling was active in HSCs in vivo and downregulated as HSCs differentiated. Inhibition of Notch signaling led to accelerated differentiation of HSCs in vitro and depletion of HSCs in vivo. Finally, intact Notch signaling was required for Wnt-mediated maintenance of undifferentiated HSCs but not for survival or entry into the cell cycle in vitro. These data suggest that Notch signaling has a dominant function in inhibiting differentiation and provide a model for how HSCs may integrate multiple signals to maintain the stem cell state. More... »

PAGES

314-322

References to SciGraph publications

  • 1998-10. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors in NATURE
  • 2000-09. arrow encodes an LDL-receptor-related protein essential for Wingless signalling in NATURE
  • 2005-04-14. Wnt signalling in stem cells and cancer in NATURE
  • 2000-09. LDL-receptor-related proteins in Wnt signal transduction in NATURE
  • 2001-01. Notch Signaling in Mammary Gland Tumorigenesis in JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
  • 2000-11. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling in NATURE MEDICINE
  • <error retrieving object. in <ERROR RETRIEVING OBJECT
  • 1999-04. β-Catenin regulates expression of cyclin D1 in colon carcinoma cells in NATURE
  • 2001-11. Stem cells, cancer, and cancer stem cells in NATURE
  • 1998-10. Drosophila Tcf and Groucho interact to repress Wingless signalling activity in NATURE
  • 2003-12-21. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor in NATURE MEDICINE
  • 2003-10. Osteoblastic cells regulate the haematopoietic stem cell niche in NATURE
  • 2003-10. Identification of the haematopoietic stem cell niche and control of the niche size in NATURE
  • 1998-08. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4 in NATURE GENETICS
  • 2003-04-27. A role for Wnt signalling in self-renewal of haematopoietic stem cells in NATURE
  • 2000-12. MAML1, a human homologue of Drosophila Mastermind, is a transcriptional co-activator for NOTCH receptors in NATURE GENETICS
  • 2000-09. An LDL-receptor-related protein mediates Wnt signalling in mice in NATURE
  • Journal

    TITLE

    Nature Immunology

    ISSUE

    3

    VOLUME

    6

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ni1164

    DOI

    http://dx.doi.org/10.1038/ni1164

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1018424763

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/15665828


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    33 schema:description A fundamental question in hematopoietic stem cell (HSC) biology is how self-renewal is controlled. Here we show that the molecular regulation of two critical elements of self-renewal, inhibition of differentiation and induction of proliferation, can be uncoupled, and we identify Notch signaling as a key factor in inhibiting differentiation. Using transgenic Notch reporter mice, we found that Notch signaling was active in HSCs in vivo and downregulated as HSCs differentiated. Inhibition of Notch signaling led to accelerated differentiation of HSCs in vitro and depletion of HSCs in vivo. Finally, intact Notch signaling was required for Wnt-mediated maintenance of undifferentiated HSCs but not for survival or entry into the cell cycle in vitro. These data suggest that Notch signaling has a dominant function in inhibiting differentiation and provide a model for how HSCs may integrate multiple signals to maintain the stem cell state.
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