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[P1–219]: PROBING DEVELOPMENTAL CONSEQUENCES OF PSEN1 MUTATIONS IN IPSC DIFFERENTIATION IN 2D AND 3D
Author(s) -
Arber Charles,
James Lovejoy Christopher Edward,
Ryan Natalie S.,
Toombs Jamie,
Willumsen Nanet,
Fox Nick C.,
Hardy John,
Wray Selina
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.039
Subject(s) - induced pluripotent stem cell , biology , reprogramming , notch signaling pathway , cellular differentiation , amyloid precursor protein , psen1 , microbiology and biotechnology , presenilin , genetics , signal transduction , embryonic stem cell , cell , alzheimer's disease , pathology , medicine , gene , disease
microfluidic device to identify growth factors regulating SKN migration. To investigate in vivo migration, fluorescentlylabelled SKNs were transplanted into the aged rat hippocampus, followed by histological analysis at three time points (day 3, 10 and 70 post-transplantation) to track their displacement, maturation and integration over time. Results: In vitro, SKNs exhibited random movements in the absence of chemoattractants, as indicated by p>0.05 in the Rayleigh test for chemotactic potential and lack of moving direction. Conversely, directed migration was induced by concentration gradients of growth factors BDNF (p<0.0001), IGF-1 (p1⁄40.0015) and VEGF (p1⁄40.0056). Calculating the Euclidean distance travelled by SKNs showed the greatest migratory potential occurred when exposed to BDNF (p<0.05) and VEGF (p<0.001). In vivo, transplanted SKNs migrated extensively over large distances by day 7 post-transplantation, with a predilection to the CA1 hippocampal subregion. Conclusions: This data demonstrates a strong migratory potential of SKNs. More importantly, despite their non-neural origin, SKNs respond to chemotactic factors known to be important for migration of endogenous hippocampal neural precursor cells, suggesting a similar migratory mechanism to hippocampal neurogenesis. This is supported by in vivo results demonstrating canine SKNs migrate extensively following transplantation, differentiating into mature neurons and populating all hippocampal subregions. Ongoing studies will identify other molecular regulators of migration and fully characterize the patter of migration in vivo.