Mouse anti-Human SPON1 monoclonal antibody, clone 4G5

It is well known that excessive drinking could result in human diseases (e.g., liver disease and cardiovascular disease). To investigate the underlying mechanisms of the effects of alcohol consumption, dental pulp stem cells have been used due to their self-renewal capability, multi-lineage differentiation, and clonogenic efficiency. Researchers usually focus on detecting genes having different mean expression levels between different conditions. However, the variance of gene expression might also provide useful information. In this study, we applied the Brown-Forsythe (BF) test for equal variance based on a human dental pulp stem cells dataset to explore the role of alcohol on the variation of gene expression. We identified two differential variable (DV) gene probes, 213597_s_at near gene CTDSPL (FDR-adjusted p-value = 1.50x10-5) and 213993_at near gene SPON1 (FDR-adjusted p-value=0.042). To best of our knowledge, no studies have found yet the associations of CTDSPL and/or SPON1 to alcohol consumption. GeneMANIA showed that these two genes are related to 20 genes. Web based gene set analysis toolkit (WebGestalt) showed that these 22 genes are enriched in 4 alcohol-related KEGG pathways: adherens junction, TGF-beta signaling pathway, signaling pathways regulating pluripotency of stem cells, and Hippo signaling pathway.

The development of midbrain dopaminergic (mDA) neurons is controlled by multiple morphogens and transcription factors. However, little is known about the role of extracellular matrix proteins in this process. Here we examined the function of roof plate-specific spondins (RSPO1-4) and the floor plate-specific, spondin 1 (SPON1). Only RSPO2 and SPON1 were expressed at high levels duringmDA neurogenesis, and the receptor LGR5 was expressed by midbrain floor plate progenitors. Surprisingly, RSPO2, but not SPON1, specifically promoted the differentiation of mDA neuroblasts into mDA neurons in mouse primary cultures and embryonic stem cells (ESCs). In addition, RSPO2 was found to promote not only mDA differentiation, but also mDA neurogenesis in human ESCs. Our results thus uncover an unexpected function of the matricellular protein RSPO2 and suggest an application to improve mDA neurogenesis and differentiation in human stem cell preparations destined to cell replacement therapy or drug discovery for Parkinson disease.