Single-Cell Transcriptomics Reveals the Molecular Logic Underlying Ca2+ Signaling Diversity in Human and Mouse Brain

The calcium ion (Ca2+) is a ubiquitous intracellular signaling molecule that plays a critical role in the adult and developing brain. However, the principles governing the specificity of Ca2+ signaling remain unresolved. In this work, we comprehensively analyzed the Ca2+ signaling transcriptome in the adult mouse brain and developing human brain. We found that neurons form non-stochastic Ca2+-states that are reflective of their cell types and functionality, with evidence suggesting that the diversity is driven by lineage-specific developmental changes. Focusing on the neocortical development, we reveal that an unprecedented number of Ca2+ genes are tightly regulated and evolutionarily conserved, capturing functionally driven differences within radial glia and neuronal progenitors. In summary, our study provides an in-depth understanding of the cellular and temporal diversity of Ca2+ signaling and suggests that Ca2+ signaling is dynamically tailored to specific cell states. One Sentence SummaryThe expression of Ca2+ signaling genes is finely tuned to cellular states, reflecting a spectrum of differences that range from lineage specificity to subtle functional distinctions within cortical radial glia.