TY - JOUR
T1 - Cochlear stem/progenitor cells from a postnatal cochlea respond to Jagged1 and demonstrate that notch signaling promotes sphere formation and sensory potential
AU - Savary, Etienne
AU - Sabourin, Jean Charles
AU - Santo, Julien
AU - Hugnot, Jean Philippe
AU - Chabbert, Christian
AU - Van De Water, Thomas
AU - Uziel, Alain
AU - Zine, Azel
PY - 2008/8/1
Y1 - 2008/8/1
N2 - 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.
AB - 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.
KW - Hair cell regeneration
KW - Hearing loss
KW - Jagged1
KW - Notch signaling
KW - Stem/progenitor cells spheres
UR - http://www.scopus.com/inward/record.url?scp=47549084224&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47549084224&partnerID=8YFLogxK
U2 - 10.1016/j.mod.2008.05.001
DO - 10.1016/j.mod.2008.05.001
M3 - Article
C2 - 18571907
AN - SCOPUS:47549084224
VL - 125
SP - 674
EP - 686
JO - Mechanisms of Development
JF - Mechanisms of Development
SN - 0925-4773
IS - 8
ER -