Cochlear stem/progenitor cells from a postnatal cochlea respond to Jagged1 and demonstrate that notch signaling promotes sphere formation and sensory potential.
Hair cells and supporting cells of the mammalian cochlea terminally differentiate during development. Recent in vitro evidence suggests the presence of hair cell progenitors in the postnatal cochlea. Phenotypic properties of these cells and factors that promote their ability to generate spheres in aggregate cultures have not been reported. We define an in vitro system that allows stem/progenitor cells harvested from the early postnatal cochlea to develop into spheres. These spheres contain Abcg2, Jagged1 and Notch1 positive progenitor cells that can divide and generate new hair cell-like cells, i.e. immunopositive for specific hair cell markers, including Myosin VI, Myosin VIIa, Math1 and ability to uptake FM1-43. We demonstrate that reducing Notch signaling with a gamma secretase inhibitor decreases the number of spheres generated following treatment of the stem/progenitor cell cultures. Additionally, activation of Notch by an exogenous soluble form of a Notch ligand, i.e. Jagged1 protein, promotes sphere formation and the sensory potential of cochlear stem/progenitor cells. Our findings suggest that Notch1/Jagged1 signaling plays a role in maintaining a population of Abcg2 sensory stem/progenitor cells in the postnatal cochlea.
Savary
Etienne
E
INSERM U583, Institute for Neurosciences of Montpellier, University of Montpellier I, 80 rue Augustin Fliche, 34091 Montpellier, Cedex 5, France.
Sabourin
Jean Charles
JC
Santo
Julien
J
Hugnot
Jean Philippe
JP
Chabbert
Christian
C
Van De Water
Thomas
T
Uziel
Alain
A
Zine
Azel
A
D000818:Animals; D002135:Calcium-Binding Proteins / Q000494:pharmacology / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003051:Cochlea / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D051880:Receptors, Notch / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D011994:Recombinant Proteins; D000072099:Serrate-Jagged Proteins