Deciphering mouse brain spatial diversity via glyco-lipidomic mapping

Abstract Gangliosides in the brain play a crucial role in modulating the integrity of vertebrate central nervous system in a region-specific manner. However, to date, a comprehensive structural elucidation of complex intact ganglioside isomers has not been achieved, resulting in the elusiveness into related molecular mechanism. Here, we present a glycolipidomic approach for isomer-specific and brain region-specific profiling of the mouse brain. Considerable region-specificity and commonality in specific group of regions are highlighted. Notably, we observe a similarity in the abundance of major isomers, GD1a and GD1b, within certain regions, which provides significant biological implications with interpretation through the lens of a theoretical retrosynthetic state-transition network. Furthermore, A glycocentric-omics approaches using gangliosides and N-glycans reveal a remarkable convergence in spatial dynamics, providing valuable insight into molecular interaction network. Collectively, this study uncovers the spatial dynamics of intact glyco-conjugates in the brain, which are relevant to regional function and accelerates the discovery of potential therapeutic targets for brain diseases.