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MicroRNAs manifest significant functions in brain neural stem cell (NSC) self-renewal and differentiation through the post-transcriptional regulation of neurogenesis genes. Let-7b is expressed in the mammalian brain and regulates NSC proliferation and differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal. Whether let-7b and TLX act as important regulators in retinal progenitor cell (RPC) proliferation and differentiation remains unknown. Here, our data show that let-7b and TLX play important roles in controlling RPC fate determination in vitro. Let-7b suppresses TLX expression to negatively regulate RPC proliferation and accelerate the neuronal and glial differentiation of RPCs. The overexpression of let-7b downregulates TLX levels in RPCs, leading to reduced RPC proliferation and increased neuronal and glial differentiation, whereas antisense knockdown of let-7b produces robust TLX expression,enhanced RPC proliferation and decreased differentiation. Moreover, the inhibition of endogenous TLX by small interfering RNA suppresses RPC proliferation and promotes RPC differentiation. Furthermore, overexpression of TLX rescues let-7b-induced proliferation deficiency and weakens the RPC differentiation enhancement caused by let-7b alone. These results suggest that let-7b, by forming a negative feedback loop with TLX, provides a novel model to regulate the proliferation and differentiation of retinal progenitors in vitro. [ABSTRACT FROM AUTHOR]

Background: The global shortage of donor corneas has motivated the development of bioengineered corneas. Although corneal endothelium has been reconstituted using corneal endothelial cells (CEC) and precursor cells with various carrier materials, all of the current options require corneal tissue and are also limited by the scarcity of donor corneas. Here, we explored the feasibility of inducing bone marrow-derived endothelial progenitor cells (BEPC) to differentiate into CEC for the repair of corneal endothelial defects. Materials and Methods: BEPC were isolated from human fetal bone marrow, and identified using several antigen markers. BEPC were cocultured with CEC for 10 days in a transwell system with conditioned medium from CEC, and cell transdifferentiation was then examined. With a porcine corneal acellular matrix (PCACM) as the carrier, the induced BEPC were transplanted onto a cat's cornea from which Descemet's membrane and the endothelium had been stripped. Results: The induced BEPC resembled CEC in polygonal shape, expressing aquaporin-1, tightly opposed cell junctions, and neurone-specific enolase. Twenty-eight days after surgery, the transparency gradually returned to the corneas transplanted with the induced BEPC on PCACM. Conclusions: Human fetal BEPC transdifferentiate into corneal endothelial-like cells in vitro. Features of the induced BEPC indicated that they may be useful for the repair of corneal endothelial dysfunction. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]