Differentiate and switch, a tale of two heads of a lipid

Abstract

Neuronal differentiation is an intricate process involving many factors and programs. One notable “curiosity” has been the observation that upon neuronal differentiation, stem cells switch the expression of their surface glycosphingolipids (GSLs) by substituting one class (the globo‐series) of GSLs by another (the ganglio‐series). Russo and colleagues show that there is an intricate dance between these two lipid series such that the globo products suppress neuronal differentiation via the master regulator AUTS2, which in turn suppresses the formation of the ganglio‐series. These findings open the door for further mechanistic studies on the roles of various GSLs in neuronal differentiation.

Figure 1. Interplay of glycosphingolipid metabolism, expression, and signaling in neuronal differentiation

The scheme shows the production of globo‐series GSLs (globosides) as the “default” preferred products of metabolism of lactosylceramides in stem like undifferentiated cells. This results in inhibition of Auts2, suppression of generation of ganglio‐series GSLs (gangliosides), and suppression of differentiation. Loss of stem cell transcription factors and/or induction of differentiation results suppression of globoside synthesis, activation of Auts2, generation of gangliosides, and induction of differentiation.