SoxC transcription factors are required for neuronal differentiation in adult hippocampal neurogenesis.

Neural stem cells (NSCs) generate new hippocampal dentate granule neurons throughout adulthood. The genetic programs controlling neuronal differentiation of adult NSCs are only poorly understood. Here we show that, in the adult mouse hippocampus, expression of the SoxC transcription factors Sox4 and Sox11 is initiated around the time of neuronal commitment of adult NSCs and is maintained in immature neurons. Overexpression of Sox4 and Sox11 strongly promotes in vitro neurogenesis from adult NSCs, whereas ablation of Sox4/Sox11 prevents in vitro and in vivo neurogenesis from adult NSCs. Moreover, we demonstrate that SoxC transcription factors target the promoters of genes that are induced on neuronal differentiation of adult NSCs. Finally, we show that reprogramming of astroglia into neurons is dependent on the presence of SoxC factors. These data identify SoxC proteins as essential contributors to the genetic network controlling neuronal differentiation in adult neurogenesis and neuronal reprogramming of somatic cells.

Olfactory ensheathing cells: attractant of neural progenitor migration to olfactory bulb.

Olfactory ensheathing cells (OECs) are the glial cells that derive from the olfactory placode, envelop olfactory axons in the course of migration from the olfactory epithelium to the olfactory bulb and reside primarily in the olfactory nerve layer. OECs transplantation as a promising experimental therapy for axonal injuries has been intensively studied; however, little is known about their roles in olfactory bulb development. In this study, we examined the effects of OECs on the migration of neural progenitors in rostral migratory stream (RMS). Initially, the neurosphere migration assay showed that OEC-conditioned medium promoted progenitors to migrate from RMS neurospheres in a concentration dependent manner. Moreover, co-culturing OECs nearby the RMS explants led to asymmetric migration of explants in different developing stages. However, OECs could influence the migration in a distance not further than 1.5 mm. Finally, slice assay that mimic the circumstance in vivo revealed that OECs had a chemoattractive activity on RMS neural progenitors. Together, these results demonstrate that OECs attract neural progenitors in RMS through the release of diffusible factors and it is likely that OECs mainly influence radial migration in the olfactory bulb but not tangential migration of the RMS invivo during development. This suggests a previously unknown function for OECs in olfactory development and a novel mechanism underlying the targeting of RMS cells.

Diffusible, membrane-bound, and extracellular matrix factors from olfactory ensheathing cells have different effects on the self-renewing and differentiating properties of neural stem cells.

Transplantation of olfactory ensheathing cells (OECs) has been a promising strategy in enhancing central nervous system (CNS) regeneration. However, little is known about the effects of transplanted OECs on the self-renewal, neurogenesis, and oligodendrogenesis of neural stem cells (NSCs), which are known to play a very important role in the repair of damaged CNS tissue. In this study, we investigated the influence of diffusible, membrane-bound, and extracellular matrix factors from OECs on the self-renewal and differentiation properties of NSCs. We found that diffusible factors from cultured OECs promoted self-renewal, whereas the extracellular matrix molecules from OECs increased neurogenesis and oligodendrogenesis of NSCs. Furthermore, we demonstrated that directly coculturing OECs and NSCs inhibited not only self-renewal but also neurogenesis and oligodendrogenesis of NSCs. We propose three models for the interaction between transplanted OECs and endogenous NSCs. Our findings provide new insight into the ability of OECs to promote CNS repair and also indicate potential targets for manipulation of these cells to enhance their restorative ability.

Olfactory ensheathing cells promote migration of Schwann cells by secreted nerve growth factor.

Transplantation of Schwann cells (SCs) and olfactory ensheathing cells (OECs) have emerged as very promising therapies for spinal cord repair. The important features of interaction between SCs and OECs are beginning to be appreciated, although the underlying mechanism remains unclear. In the present study, we tested the effects of OECs on SCs migration using a range of in vitro migration assays. We found that SCs migrated abundantly upon OECs monolayer, and the migration-promoting effects were identified to be due to the secreted diffusible factors in OEC-derived conditioned medium (OEC-CM). Furthermore, neutralizing nerve growth factor (NGF) in OEC-CM with NGF antibody could block this effect. Moreover, we found that NGF promotes SCs migration even on astrocyte monolayer. Taken together, these findings provide the first evidence that OECs can promote SCs migration in astrocytic environment by secreted NGF.