Ciliary neurotrophic factor-mediated signaling regulates neuronal versus glial differentiation of retinal stem cells/progenitors by concentration-dependent recruitment of mitogen-activated protein kinase and Janus kinase-signal transducer and activator of transcription pathways in conjunction with Notch signaling.

In the retina, as elsewhere in the central nervous system, neurogenesis precedes gliogenesis; that is, the only glia in the retina, Müller cells, are born when the majority of neurons have already been generated. However, our understanding of how the multipotent retinal stem cells/progenitors choose to differentiate along neuronal and glial lineages is unclear. This information is important in promoting directed differentiation of retinal stem cells/progenitors in an ex vivo or in vivo stem cell approach to treating degenerative retinal diseases.

Derivation of neurons with functional properties from adult limbal epithelium: implications in autologous cell therapy for photoreceptor degeneration.

The limbal epithelium (LE), a circular and narrow epithelium that separates cornea from conjunctiva, harbors stem cells/progenitors in its basal layer that regenerate cornea. We have previously demonstrated that cells in the basal LE, when removed from their niche and cultured in reduced bond morphogenetic protein signaling, acquire properties of neural progenitors. Here, we demonstrate that LE-derived neural progenitors generate neurons with functional properties and can be directly differentiated along rod photoreceptor lineage in vitro and in vivo.

RNF2 interacts with the linker region of the human P-glycoprotein.

The human P-glycoprotein (Pgp) is a drug-efflux pump responsible for innate or acquired multidrug resistance in many cancers. Pgp contains a unique approximately 75 amino acid long linker region in its middle, which is critically important for its drug transport and ATPase functions. To identify cellular proteins that bind to this linker region and modulate Pgp function, a yeast two-hybrid analysis was carried out.

Neural stem cell properties of Müller glia in the mammalian retina: regulation by Notch and Wnt signaling.

The retina in adult mammals, unlike those in lower vertebrates such as fish and amphibians, is not known to support neurogenesis. However, when injured, the adult mammalian retina displays neurogenic changes, raising the possibility that neurogenic potential may be evolutionarily conserved and could be exploited for regenerative therapy. Here, we show that Müller cells, when retrospectively enriched from the normal retina, like their radial glial counterparts in the central nervous system (CNS), display cardinal features of neural stem cells (NSCs), i.

Characterization of a new antibody raised against the NH2 terminus of P-glycoprotein.

Purpose: Cancers exposed to chemotherapy develop multidrug resistance, a major cause for chemotherapy failure. One mechanism of multidrug resistance development is due to overexpression of P-glycoprotein (Pgp) in these cancer cells. Thus, a prechemotherapy evaluation of Pgp in cancer cells aids in the design of alternative regimens that can circumvent such failure.