Adult Neural Stem Cells from Midbrain Periventricular Regions Show Limited Neurogenic Potential after Transplantation into the Hippocampal Neurogenic Niche.

Mareike Fauser,Alexander Storch,Johannes Rangnick,Moritz D Brandt,Andreas Hermann,Kai F Loewenbrück

doi:10.3390/cells10113021

Mareike Fauser, Alexander Storch + Show 4 more

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https://doi.org/10.3390/cells10113021

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Abstract

The regulation of adult neural stem or progenitor cell (aNSC) proliferation and differentiation as an interplay of cell-intrinsic and local environmental cues remains in part unclear, impeding their role in putative regenerative therapies. aNSCs with all major properties of NSCs in vitro have been identified in a variety of brain regions beyond the classic neurogenic niches, including the caudal periventricular regions (PVRs) of the midbrain, though active neurogenesis is either limited or merely absent in these regions. To elucidate cell-intrinsic properties of aNSCs from various PVRs, we here examined the proliferation and early differentiation capacity of murine aNSCs from non-neurogenic midbrain PVRs (PVRMB) compared to aNSCs from the neurogenic ventricular-subventricular zone (PVRV-SVZ) 7 days after transplantation into the permissive pro-neurogenic niche of the dentate gyrus (DG) of the hippocampus in mice. An initial in vitro characterization of the transplants displayed very similar characteristics of both aNSC grafts after in vitro expansion with equal capacities of terminal differentiation into astrocytes and Tuj1+ neurons. Upon the allogenic transplantation of the respective aNSCs into the DG, PVRMB grafts showed a significantly lower graft survival and proliferative capacity compared to PVRV-SVZ transplants, whereby the latter are exclusively capable of generating new neurons. Although these differences might be—in part—related to the transplantation procedure and the short-term study design, our data strongly imply important cell-intrinsic differences between aNSCs from neurogenic compared to non-neurogenic PVRs with respect to their neurogenic potential and/or their sensitivity to neurogenic cues.

Highlights

Adult neurogenesis is a well-known phenomenon that occurs in two distinct germinal niches of the rodent brain: the ventricular-subventricular zone (V-SVZ) within the periventricular regions of the lateral wall of the lateral ventricles (PVRV-SVZ) and the dentate gyrus (DG) of the hippocampus
These differences might be—in part—related to the transplantation procedure and the short-term study design, our data strongly imply important cell-intrinsic differences between adult neural stem or progenitor cell (aNSC) from neurogenic compared to non-neurogenic PVRs with respect to their neurogenic potential and/or their sensitivity to neurogenic cues
Within the PVRV-SVZ, the cellular cascade leading to the formation of new neurons has been extensively studied with subependymal glial fibrillary acidic protein+ (GFAP+) astrocytes identified as the genuine adult neural stem cells

Summary

Introduction

Adult neurogenesis is a well-known phenomenon that occurs in two distinct germinal (neurogenic) niches of the rodent brain: the ventricular-subventricular zone (V-SVZ) within the periventricular regions of the lateral wall of the lateral ventricles (PVRV-SVZ) and the dentate gyrus (DG) of the hippocampus. Within the PVRV-SVZ, the cellular cascade leading to the formation of new neurons has been extensively studied with subependymal glial fibrillary acidic protein+ (GFAP+) astrocytes identified as the genuine adult neural stem cells (aNSCs). They generate—through various intermediate stages—distinct subtypes of interneurons determined to integrate into different cell layers in the olfactory bulb, where they are involved in olfactory learning processes (for a review, see [1]). Epigenetic regulation through chromatin modification [12], histone acetylation [13] and DNA methylation [14] seems important

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