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The Journal of Neuroscience, June 23, 2004, 24(25):5670-5683; doi:10.1523/JNEUROSCI.0330-04.2004

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Cellular/Molecular
Olfactory Horizontal Basal Cells Demonstrate a Conserved Multipotent Progenitor Phenotype

Lindsay A. Carter, Jessica L. MacDonald, and A. Jane Roskams

Department of Zoology and Center for Molecular Medicine and Therapeutics, University of British Columbia, V6T 1Z4 Vancouver, Canada

Stem cells of adult regenerative organs share a common goal but few established conserved mechanisms. Within the neural stem cell niche of the mouse olfactory epithelium, we identified a combination of extracellular matrix (ECM) receptors that regulate adhesion and mitosis in non-neural stem cells [intercellular adhesion molecule-1 (ICAM-1), ₁, ₄, and -1, -3, and -6 integrins] and on horizontal basal cells (HBCs), candidate olfactory neuro-epithelial progenitors. Using ECM receptors as our guide, we recreated a defined microenvironment in vitro that mimics olfactory basal lamina and, when supplemented with epidermal growth factor, transforming growth factor , and leukemia inhibitory factor, allows us to preferentially expand multiple clonal adherent colony phenotypes from individual ICAM-1+ and ICAM-1+/₁ integrin+-selected HBCs. The most highly mitotic colony-forming HBCs demonstrate multipotency, spontaneously generating more ICAM-positive presumptive HBCs, a combination of olfactory neuroglial progenitors, and neurons of olfactory and potentially nonolfactory phenotypes. HBCs thus possess a conserved adhesion receptor expression profile similar to non-neural stem cells, preferential self-replication in an in vitro environment mimicking their in vivo niche, and contain subpopulations of cells that can produce multiple differentiated neuronal and glial progeny from within and beyond the olfactory system in vitro.

View larger version (79K): [in this window] [in a new window]   Figure 9. Factors that regulate the interaction of progenitor subtypes in the olfactory epithelium. HBCs can self renew (size of curved arrow indicates capacity to divide-self-renew) and exist in a tightly adherent and loosely adherent (HBC*) mitotic phenotypes, which are differentiated by their expression levels of ICAM-1 (yellow) and and integrin complexes (orange arrows). A more restricted neuronal-sustentacular (SUS) progenitor is found in the GBC population, whereas a gliogenic precursor can also be derived from mitotic HBCs. ECM gradients for laminin, collagen, and fibronectin are indicated, along with the factors that combine with matrix stimulation to positively regulate the balance between progenitor subtypes and immature and mature cells within the OE and lamina propria. Inset simplifies the relationship between different OE progenitor subtypes, where B (GBC) and C (OEC-GRPs) reside in entirely different ECM, cell-cell, and growth factor environments within the OE and lamina propria.

 

Key words: degeneration; development; olfactory; progenitor; extracellular matrix; gliogenesis

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Received Jan 29, 2004; revised April 18, 2004; accepted May 6, 2004.

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