Single-nulceus RNA sequencing of human-induced neuron and astrocytes treated with cell-secreted amyloid beta peptides

In this work, we investigated the early effects of Aβ peptides accumulation on gene expression profiles of human-induced neurons (hiNs). Using single-cell RNA sequencing, we show that cell-secreted Aβ up-regulates the expression of several synaptic-related genes and down-regulates the expression of genes associated with metabolic stress mainly in glutamatergic neurons and to a lesser degree in GABAergic neurons and astrocytes. These neuronal alterations correlate with activation of SEMA5, EPHA and NECTIN signaling pathways, which are important regulators of synaptic plasticity. Altogether, our findings indicate that slight elevations in Aβ concentrations are sufficient to elicit transcriptional changes in human neurons that can contribute to early alterations on neural network activity.

Count table showing the number of counts per nucleus in 6-week-old human-induced neurons and astrocytes treated with conditioned media from CHO cell lines overexpressing the human APP695 (CHO-APPWT) or the London mutated APP695 (CHO-APPV717L) (Guillot-Sestier et al., 2012) or non-conditioned medium (Blank/control) . Metadata file associated with count table.