Astro-logics with microRNAs

Abstract

Astrocytes are a subtype of glial cells in the central nervous system that are critical for normal brain activity. In this issue of The EMBO Journal, Shenoy et al provide evidence for the involvement of miRNAs in the molecular mechanism underlying the in vitro differentiation of astrocytes from glial progenitor cells. Let-7 and miR-125 jointly silence multiple mRNA targets that would have potentially disrupted differentiation if expressed, and function in concert with JAK-STAT signaling to promote astrocyte differentiation.

Figure 1. miRNAs enable in vitro differentiation of astrocytes in concert with JAK-STAT signaling

(A) Diagram describing the mechanism identified by Shenoy et al (2015), for in vitro differentiation of glial progenitor cells into astrocytes; JAK-STAT signaling initiates transcription of astrocyte-specific mRNAs and functions in concert with miR-125 and Let-7. The miRNAs serve to silence the expression of mRNAs that are disallowed, in the sense that they block astrocyte differentiation. (B) JAK-STAT signaling maintains pluripotency of embryonic stem cells and is opposed by Let-7 that promotes differentiation. However, in the context of glial progenitor cells, these two mechanisms act cooperatively to enable astrocyte differentiation. The changing transcriptional landscape that provides the miRNAs with altered set of targets is probably an important element in the ability to provide different context for miRNA activity in different cells.