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bioRxiv · 10.1101/2020.06.08.140467

Evidence of progenitor cell lineage rerouting in the adult mouse hippocampus

Moura, D. M. S.·Brandao, J. A.·Lentini, C.·Heinrich, C.·Queiroz, C. M.·Costa, M. R.
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Abstract

Cell lineage in the adult hippocampus comprises multipotent and neuron-committed progenitors. In the present work, we fate-mapped neuronal progenitors using Dcx-CreERT2 and CAG-CAT-EGFP double-transgenic mice (cDCX/EGFP). We show that three days after tamoxifen-mediated recombination in cDCX/EGFP adult mice, GFP+ cells in the dentate gyrus co-expresses DCX and about 6% of these cells are proliferative neuronal progenitors. After 30 days, 20% of GFP+ generated from these progenitors differentiate into GFAP+ astrocytes. Administration of the chemoconvulsants kainic acid (KA) or pilocarpine (PL) led to a significant increase in the number of GFP+ cells in both ipsi and contralateral dentate gyrus. However, while PL favored the differentiation of neurons in both ipsi- and contralateral sides, KA stimulated neurogenesis only in the contralateral side. In the ipsilateral side, KA injection led to an unexpected increase of astrogliogenesis in the Dcx-lineage. These different effects of KA and PL in the Dcx-lineage are associated with distinct alterations of the parvalbuminergic plexus and inflammatory responses in the hippocampi. Finally, we also observed a small number of GFP+/GFAP+ cells displaying radial-glia morphology ipsilaterally 3 days after KA administration, indicating that Dcx-progenitors could regress to a multipotent stage. Altogether, our data suggest that cell lineage in the adult hippocampus is not unidirectional and can be modulated by environmental signals.

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Moura, D. M. S., Brandao, J. A., Lentini, C., Heinrich, C., Queiroz, C. M., Costa, M. R.. 2020-06-09. Evidence of progenitor cell lineage rerouting in the adult mouse hippocampus. https://doi.org/10.1101/2020.06.08.140467

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