Single-cell analysis reveals T cell infiltration in old neurogenic niches

Neurogenic niches are important spots into the brain in which neural stem cells and other homeostatic populations harbour, and in which neurogenesis takes place. One of their well-renown limits is represented by the fact that, as years pass by, niches become less-functional, and neural regeneration becomes less efficient. RNA sequencing-based single-cell analysis, performed by Dulken and collaborators, individuated, for the first time, a clonally-expanded population of CD8+ T cells in older mice that might be responsible of loss of efficiency of the neural progenitors in the niches. These lymphocytes display a different transcriptomic fingerprint from those found in the periphery, they are almost absent in younger animals and express gamma-interferon (IFNg), by means of which they seem to be able to suppress proliferation in the interferon-responding neurons of the neurogenic niches.

The authors used BTS2, the mouse orthologous gene of human tetherin, as a surface marker to individuate interferon response signature in niche-resident activated neural stem cells (aNSCs) and neural progenitor cells (NPCs). BTS2-expressing aNSCs/NPCs from old mice displayed significant depletion of cell cycle-related mRNAs, indicating that they were less prone to replicate and initiate neurogenesis in presence of IFNg-producing cells. This was further corroborated by the fact that higher amounts of BTS2-expressing cells in neurogenic niches correlated with the amount of T cells, while experimentally-induced entry of CD8+ T cells in the brain enhanced the amounts of BTS2-positive neuron progenitors, as well as reducing their proliferative capacity.

Source: Nature

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