Multimodal Single-Cell Analysis Reveals Physiological Maturation in the Developing Human Neocortex
| Autor: | Diane Jung, Carlos E. Cunha, Georgia Panagiotakos, Nils Lovegren, Andreas Mayer, Anne A. Leyrat, Jay A. A. West, Michael L. Gonzales, Arturo Alvarez-Buylla, Lukasz Szpankowski, Tomasz J. Nowakowski, Beatriz Alvarado, Dmitry Velmeshev, Jiadong Chen, Simone Mayer, Ugomma C. Eze, Arnold R. Kriegstein, Emmy Li, Mercedes F. Paredes, Shaohui Wang, Aparna Bhaduri, Arpana Arjun, Alex A. Pollen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
radial glia Neocortex Transcriptome Mice radial glia scaffold Substance Misuse 0302 clinical medicine Single-cell analysis 5-HT2A Psychology Receptor Serotonin 5-HT2A Developmental Pediatric General Neuroscience Neurogenesis Gene Expression Regulation Developmental Brain differentiation Cell biology calcium imaging medicine.anatomical_structure Stem Cell Research - Nonembryonic - Non-Human Cognitive Sciences Single-Cell Analysis Sequence Analysis Receptor neurotransmitter Cell type Serotonin human neocortical development 1.1 Normal biological development and functioning Ependymoglial Cells Biology Article single-cell RNA sequencing 03 medical and health sciences Calcium imaging Neurotransmitter receptor Underpinning research medicine Animals Humans Cell Lineage Progenitor cell Neurology & Neurosurgery Sequence Analysis RNA Gene Expression Profiling intermediate progenitor cells Neurosciences Stem Cell Research 030104 developmental biology Gene Expression Regulation RNA Calcium 030217 neurology & neurosurgery |
| Zdroj: | Neuron, vol 102, iss 1 Neuron |
| Popis: | 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 diversitynot captured by single-cell transcriptomics. We find that the serotonin receptor HTR2A selectively activates radial glia cells in the developing human, butnot mouse, neocortex, and inhibiting HTR2A receptorsin human radial glia disrupts the radial glial scaffold. We show highly specific neurotransmittersignaling during neurogenesis in the developing human neocortex and highlight evolutionarilydivergent mechanisms of physiological signaling. |
| Databáze: | OpenAIRE |
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