Human PSEN1 Mutant Glia Improve Spatial Learning and Memory in Aged Mice

PSEN1 ΔE9 mutation causes a familial form of Alzheimer's disease. We have previously shown that human induced pluripotent stem cell (iPSC)-derived astrocytes carrying PSEN1 ΔE9 mutation exhibit transcriptional and functional abnormalities (Stem Cell Reports. 2017;9:1885-1897). Here we injected glial progenitors derived from 2 pairs of PSEN1 ΔE9 mutant- isogenic CTRL iPSCs intracerebroventricularly into newborn mice. At the age of 18 months, mouse hippocampi containing human cells (5 x PSEN1 ΔE9 + 6 x CTRL, all from male mice) were quickly dissected out and bulk RNA sequencing analysis was performed. Our results shed more light on the efffect of PSEN1 ΔE9 mutation on human glia in vivo as well as on the effect of the presence of mutant human glia on the surrounding healthy mouse cells. Human iPSC-derived glial progenitors were injected intracerebroventricularly into newborn immunedeficient mice and were let to proliferate and maturate in the mouse brain for 18 months. Ribo-depleted RNA was then sequenced with Illumina Next-seq 500 from mouse hippocampi containing human cells (5 x PSEN1 ΔE9 + 6 x CTRL). Sequences from human and mouse origin were analyzed separately.