GSE49023
Mouse ES-derived motor neurons (ES-MN) exposed to SOD1 mutant mouse astrocyte conditioned media
This datased was used to obtain a genome-wide expression signature for the early response of mouse motor neurons to mutant SOD1 astrocytes conditioned media. Neurons, far from living in isolation, are surrounded by a host of other neuronal and non-neuronal cells, such as astrocytes. The latter entertain complex functional interactions with neighboring neurons, which, under normal conditions, are important for the their well-being. In pathological situations, however, altered astrocyte behavior may contribute to the demise of neighboring neurons. Such non-cell autonomous pathogenic scenario is increasingly considered in a variety of disorders, including amyotrophic lateral sclerosis (ALS), the most frequent adult-onset paralytic disorder. Assembly and interrogation of gene regulatory models has helped elucidate causal mechanisms responsible for the presentation of several tumor-related phenotypes. To systematically elucidate the effectors of neurodegeneration in a model of ALS, we first developed techniques for the efficient purification of motor neurons (MNs), the primary target of ALS neurodegenerative process. We then generated gene expression profiles to fully characterize the critical timepoints associated with initiation and commitment of MN degenerative progression in an in vitro murine mutant SOD1 (mSOD1) model of ALS. Overall design: ES cells were derived from transgenic Hlxb9-GFP1Tmj mice expressing eGFP and CD2 driven by the mouse HB9 promoter. These cells were then differentiated into motor neurons (ES-MN) as described previously [PMID 12176325] ES-MN were exposed to non-transgenic (NTg), G93A mutant SOD1 (mSOD1) or wtSOD1 over-expression astrocytes conditioned media for 0 days (time zero control), 1 day, and 3 days. Total RNA was extracted and profiled by RNAseq.