Non-proliferative adult neurogenesis in neural crest-derived stem cells isolated from human periodontal ligament

Abstract

Self-renewal and lineage regulation of neural stem cells in the adult mammalian brain (aNSCs) are still far from been understood. Although previous studies have reported that some aNSCs in neurogenic niches showed irregular nuclei, their functional significance remains elusive. We used neural crest-derived human periodontal ligament stem cells (hPDLSCs) as an in vitro cell model of neurogenesis to investigate the functional significance of nuclear polymorphisms. Here, we show that hPDLSCs-derived neurons are not directly generated through cell division from stem cells. In fact, the cell shape of neural precursors is reset and start their neuronal development as round spheres. The hPDLSCs-derived neurons gradually adopted a complex morphology adquiring dendritic-like and axonal-like identities, giving rise to a variety of neuron-like morphologies. We have discovered a transient cell nuclei lobulation coincident to in vitro neurogenesis, without being related to cell proliferation. We observed that small DNA containing structures move within the cell and temporarily form lobed nuclei.Morphological analysis also reveals that neurogenic niches in the adult mouse brain contains cells with nuclear shapes highly similar to those observed during in vitro neurogenesis from hPDLSCs. Our results provide evidence that neuronal differentiation from aNSCs may also occur during in vivo adult mammalian neurogenesis without being related to cell proliferation. In addition, we demonstrate that hPDLSCs-derived neurons display a sequence of morphologic development highly similar to those observed in primary neuronal cultures derived from rodent brains during neurogenesis, providing evidence that it is possible to reproduce neurogenic processes and obtain neurons from hPDLSCs.