Abstract
Cell diversity of the brain and how it is affected by starvation, remains largely unknown. Here, we introduce a single cell transcriptome atlas of the entire Drosophila first instar larval brain. We first assigned cell-type identity based on known marker genes, distinguishing five major groups: neural progenitors, differentiated neurons, glia, undifferentiated neurons and non-neural cells. All major classes were further subdivided into multiple subtypes, revealing biological features of various cell-types. We further assessed transcriptional changes in response to starvation at the single-cell level. While after starvation the composition of the brain remains unaffected, transcriptional profile of several cell clusters changed. Intriguingly, different cell-types show very distinct responses to starvation, suggesting the presence of cell-specific programs for nutrition availability. Establishing a single-cell transcriptome atlas of the larval brain provides a powerful tool to explore cell diversity and assess genetic profiles from developmental, functional and behavioral perspectives.
Highlights
The brain, as the central organ of the nervous system, shows high complexity and diversity of celltypes
We dissected the central nervous system (CNS) of late first instar larvae and separated the brain lobes from the ventral nerve cord (VNC) to enrich for cells populating the larval brain (Figure 1A)
In close vicinity with these cells, another population of neuropeptide-producing cells is involved in the secretion of the Prothoracicotropic hormone (Ptth). We mapped these cells to our dataset and we found that this gene was not being transcribed at high levels, compared to other neuropeptides, but it was present in the larval brain (Figure 4C)
Summary
The brain, as the central organ of the nervous system, shows high complexity and diversity of celltypes. The cells populating the larval brain develop from neuroblasts delaminated from the procephalic neurectoderm, during early embryonic stages. Neuroblasts will re-enter proliferation and generate different cell-types that form the adult brain. During these steps, nutrient accessibility plays a key role. It has been previously described that some glial cells, in close proximity to the neuroblast populations, release insulin-like peptides upon nutrient-sensing. This signal is later incorporated by neuroblasts through the InR/PI3K/TORC1 pathway, to induce reactivation and exit from quiescence (Chell and Brand, 2010; Sousa-Nunes et al, 2011). Identifying genetic responses during brain development in normal feeding condition versus starvation may allow a better and more complete understanding of the processes regulated by the intake of nutrients at early life stages
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