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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Mayer, S; Chen, J; Velmeshev, D; Mayer, A; Eze, UC; Bhaduri, A; Cunha, CE; Jung, D; Arjun, A; Li, E; Alvarado, B; Wang, S; Lovegren, N; Gonzales, ML; Szpankowski, L; Leyrat, A; West, JAA; Panagiotakos, G; Alvarez-Buylla, A; Paredes, MF; Nowakowski, TJ; Pollen, AA; Kriegstein, AR

Published Date

  • April 3, 2019

Published In

Volume / Issue

  • 102 / 1

Start / End Page

  • 143 - 158.e7

PubMed ID

  • 30770253

Pubmed Central ID

  • PMC7648658

Electronic International Standard Serial Number (EISSN)

  • 1097-4199

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2019.01.027


  • eng

Conference Location

  • United States