According to new research findings from the Eaton-Peabody Laboratories at Massachusetts Eye and Ear, Harvard Medical School, and Fudan University in Shanghai, China, blocking the Notch pathway that controls hair cell distribution in the inner ear may help determine cochlear progenitor cell proliferation capacity. In a study article, which was published in a December 2014 online edition of the PNAS journal, the researchers report that the postnatal mammalian inner ear harbors progenitor cells which have the potential for hair cell regeneration and hearing recovery, but the mechanisms that control their proliferation and hair cell regeneration are yet to be determined. With this recent study, the researchers say, they have learned something new about the mechanisms of cell division and hair cell regeneration.
“A high level of Notch activity prevents progenitor cell division and hair cell regeneration in the postnatal inner ear,” said Zhen-Yi Chen, PhD, of the Eaton-Peabody Laboratories at Massachusetts Eye and Ear, and associate professor of otology and laryngology at Harvard Medical School. “It is known that inhibition of Notch activity can convert inner ear supporting cells to hair cells. In this paper, we have shown that Notch inhibition also promotes cell division. Under the condition, the inner ear progenitor cells re-enter cell division to regenerate hair cells in postnatal cochlea.”
The researchers showed in their study that Notch inhibition initiates proliferation of supporting cells that give rise to new hair cells in postnatal mouse cochlea in vivo and in vitro. Through lineage tracing, they identified that a majority of the proliferating supporting cells and cell division-generated hair cells induced by Notch inhibition are originated from the Wnt-responsive leucine-rich repeat-containing G protein coupled receptor 5 (Lgr5+) progenitor cells. They demonstrated that Notch inhibition removes the brakes on the canonical Wnt signaling and promotes Lgr5+ progenitor cells to mitotically generate new hair cells.
Dr Chen says that this study provides a potential route for blocking Notch activity to increase progenitor cell population by cell division, and to regenerate new hair cells. According to Dr Chen, their work could lead to developing new strategies to achieve hair cell regeneration for hearing restoration.
Source: Eaton-Peabody Laboratories at Massachusetts Eye and Ear, Harvard Medical School, and PNAS