Orthis Saha, Ana Raquel Melo de Farias, Alexandre Pelletier, Dolores Siedlecki-Wullich, Bruna Soares Landeira, Johanna Gadaut, Arnaud Carrier, Anaïs-Camille Vreulx, Karine Guyot, Yun Shen, Amelie Bonnefond, Philippe Amouyel, Julia Tcw, Devrim Kilinc, Claudio Marcos Queiroz, Fabien Delahaye, Jean-Charles Lambert, Marcos R Costa
Bridging Integrator 1 (BIN1) is the second most important Alzheimer's disease (AD) risk gene, but its physiological roles in neurons and its contribution to brain pathology remain largely elusive. In this work, we show that BIN1 plays a critical role in the regulation of calcium homeostasis, electrical activity, and gene expression of glutamatergic neurons. Using single-cell RNA-sequencing on cerebral organoids generated from isogenic BIN1 wild type (WT), heterozygous (HET) and homozygous knockout (KO) human-induced pluripotent stem cells (hiPSCs), we show that BIN1 is mainly expressed by oligodendrocytes and glutamatergic neurons, like in the human brain...
March 22, 2024: Molecular Psychiatry