Hs3st2 loss of function in primary hippocampal neurons from the rTg4510 mouse
The objective of the study was to compare the transcriptomic landscape of cultured hippocampal neurons from rTg4510 mouse model of tauopathy (Tg) following Hs3st2 loss of function (LOF) and vs wild-type (WT) cells from Tg littermates. The rTg4510 mouse overexpresses a repressible form of human tau carrying the P301L mutation. Tau expression is controlled by a tetracycline-responsive element (tetO) and activated by a forebrain-specific transactivator under the CaMKIIalpha promoter. In the absence of doxycycline, tau expression is induced primarily in the hippocampus and cortex, leading to progressive tau hyperphosphorylation, neurofibrillary tangle formation, neuronal loss, and cognitive deficits, recapitulating key features of human tauopathies, including frontotemporal dementia and Alzheimer's disease. Hs3st2 is a sulfotransferase predominantly expressed in neurons. This enzyme catalyzes the addition of sulfate groups at the C3 position of specific glucosamine residues in heparan sulfate chains. The biological processes affected by the inhibition of Hs3st2 expression in neurons affected by tau pathology remain unknown. Thus, this study aims to provide transcriptomic data to address this question in rTg4510 embryonic (E16)-derived primary hippocampal neurons. Lentiviral (Lv) particles carrying shHs3st2 (LvHs3st2) and control empty particles (Lv) were used to treat Tg neurons for 5 days in vitro (DIV). Transcriptomic seq analysis was performed in RNA extracts to compare WT vs Tg neurons and Tg vs Tg-Hs3st2-LOF.