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Publication

Multimodal Single-Cell Analysis Reveals Physiological Maturation in the Developing Human Neocortex.

Neuron | 2019

In the developing human neocortex, progenitor cells generate diverse cell types prenatally. Progenitor cells and newborn neurons respond to signaling cues, including neurotransmitters. While single-cell RNA sequencing has revealed cellular diversity, physiological heterogeneity has yet to be mapped onto these developing and diverse cell types. By combining measurements of intracellular Ca2+ elevations in response to neurotransmitter receptor agonists and RNA sequencing of the same single cells, we show that Ca2+ responses are cell-type-specific and change dynamically with lineage progression. Physiological response properties predict molecular cell identity and additionally reveal diversity not captured by single-cell transcriptomics. We find that the serotonin receptor HTR2A selectively activates radial glia cells in the developing human, but not mouse, neocortex, and inhibiting HTR2A receptors in human radial glia disrupts the radial glial scaffold. We show highly specific neurotransmitter signaling during neurogenesis in the developing human neocortex and highlight evolutionarily divergent mechanisms of physiological signaling.

Pubmed ID: 30770253 RIS Download

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Associated grants

Agency: NIMH NIH HHS, United States
Id: U01 MH114825
Agency: NINDS NIH HHS, United States
Id: R35 NS097305
Agency: NIMH NIH HHS, United States
Id: U01 MH105989
Agency: NINDS NIH HHS, United States
Id: K08 NS091537
Agency: NICHD NIH HHS, United States
Id: T32 HD007470
Agency: Medical Research Council, United Kingdom
Id: MR/R006237/1

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