| Endothelial type I interferon signaling modulates the vascular response to ischemic brain injury |
Kavli Affiliate: Shai Shaham
| Authors: Simin Liu, Kenneth Bradley, Jinghong J. Tang, Yoon A. Kim, Ana Milosevic and Shai Shaham
| Summary:
Astrocytic glia regulate brain assembly, synapse formation/activity, neuronal energetics, and brain metabolism. Gene programs driving astrocyte specification are only partly understood. Here, we use lineage-restricted single-cell RNA sequencing to uncover a two-phase developmental program for C. elegans CEPsh astrocyte differentiation. In phase one, newly generated astrocytes acquire common transcription profiles despite arising from lineally and transcriptionally distinct progenitors. Convergent differentiation is mediated by the distal-less transcription factor CEH-43. CEH-43 is expressed in astrocytes and their progenitors, binds conserved astrocyte-expressed genes, and cell-autonomously controls astrocyte-specific gene expression. Forced misexpression of CEH-43 in the embryo promotes ectopic expression of astrocyte-specific reporters. The second gene expression phase, directing astrocyte maturation, is also under CEH-43 control. Homologs of CEPsh astrocyte-enriched genes are preferentially enriched in mammalian astrocytes, and the CEH-43 homologs DLX1/2 are expressed in mouse astrocytes. Our findings suggest parallels between CEPsh and mammalian astrocyte development, implicating conserved regulators in astrocyte cell-fate acquisition.