Multimodal Single-Cell Analysis Reveals Physiological Maturation in the Developing Human Neocortex. Mayer, S., Chen, J., Velmeshev, D., Mayer, A., Eze, U. C, Bhaduri, A., Cunha, C. E, Jung, D., Arjun, A., Li, E., Alvarado, B., Wang, S., Lovegren, N., Gonzales, M. L, Szpankowski, L., Leyrat, A., West, J. A A, Panagiotakos, G., Alvarez-Buylla, A., Paredes, M. F, Nowakowski, T. J, Pollen, A. A, & Kriegstein, A. R Neuron, 102(1):143–158.e7, February, 2019. abstract bibtex 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 Ca(2+) elevations in response to neurotransmitter receptor agonists and RNA sequencing of the same single cells, we show that Ca(2+) 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.
@ARTICLE{Mayer2019-tl,
title = "Multimodal {Single-Cell} Analysis Reveals Physiological
Maturation in the Developing Human Neocortex",
author = "Mayer, Simone and Chen, Jiadong and Velmeshev, Dmitry and Mayer,
Andreas and Eze, Ugomma C and Bhaduri, Aparna and Cunha, Carlos E
and Jung, Diane and Arjun, Arpana and Li, Emmy and Alvarado,
Beatriz and Wang, Shaohui and Lovegren, Nils and Gonzales,
Michael L and Szpankowski, Lukasz and Leyrat, Anne and West, Jay
A A and Panagiotakos, Georgia and Alvarez-Buylla, Arturo and
Paredes, Mercedes F and Nowakowski, Tomasz J and Pollen, Alex A
and Kriegstein, Arnold R",
abstract = "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 Ca(2+) elevations in response to neurotransmitter
receptor agonists and RNA sequencing of the same single cells, we
show that Ca(2+) 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.",
journal = "Neuron",
volume = 102,
number = 1,
pages = "143--158.e7",
month = feb,
year = 2019,
keywords = "calcium imaging; differentiation; human neocortical development;
intermediate progenitor cells; neurogenesis; neurotransmitter;
radial glia; radial glia scaffold; serotonin; single-cell RNA
sequencing",
language = "en"
}
Downloads: 0
{"_id":"rWpvAYTCHbs5aWh3J","bibbaseid":"mayer-chen-velmeshev-mayer-eze-bhaduri-cunha-jung-etal-multimodalsinglecellanalysisrevealsphysiologicalmaturationinthedevelopinghumanneocortex-2019","author_short":["Mayer, S.","Chen, J.","Velmeshev, D.","Mayer, A.","Eze, U. C","Bhaduri, A.","Cunha, C. E","Jung, D.","Arjun, A.","Li, E.","Alvarado, B.","Wang, S.","Lovegren, N.","Gonzales, M. L","Szpankowski, L.","Leyrat, A.","West, J. A A","Panagiotakos, G.","Alvarez-Buylla, A.","Paredes, M. F","Nowakowski, T. J","Pollen, A. A","Kriegstein, A. R"],"bibdata":{"bibtype":"article","type":"article","title":"Multimodal Single-Cell Analysis Reveals Physiological Maturation in the Developing Human Neocortex","author":[{"propositions":[],"lastnames":["Mayer"],"firstnames":["Simone"],"suffixes":[]},{"propositions":[],"lastnames":["Chen"],"firstnames":["Jiadong"],"suffixes":[]},{"propositions":[],"lastnames":["Velmeshev"],"firstnames":["Dmitry"],"suffixes":[]},{"propositions":[],"lastnames":["Mayer"],"firstnames":["Andreas"],"suffixes":[]},{"propositions":[],"lastnames":["Eze"],"firstnames":["Ugomma","C"],"suffixes":[]},{"propositions":[],"lastnames":["Bhaduri"],"firstnames":["Aparna"],"suffixes":[]},{"propositions":[],"lastnames":["Cunha"],"firstnames":["Carlos","E"],"suffixes":[]},{"propositions":[],"lastnames":["Jung"],"firstnames":["Diane"],"suffixes":[]},{"propositions":[],"lastnames":["Arjun"],"firstnames":["Arpana"],"suffixes":[]},{"propositions":[],"lastnames":["Li"],"firstnames":["Emmy"],"suffixes":[]},{"propositions":[],"lastnames":["Alvarado"],"firstnames":["Beatriz"],"suffixes":[]},{"propositions":[],"lastnames":["Wang"],"firstnames":["Shaohui"],"suffixes":[]},{"propositions":[],"lastnames":["Lovegren"],"firstnames":["Nils"],"suffixes":[]},{"propositions":[],"lastnames":["Gonzales"],"firstnames":["Michael","L"],"suffixes":[]},{"propositions":[],"lastnames":["Szpankowski"],"firstnames":["Lukasz"],"suffixes":[]},{"propositions":[],"lastnames":["Leyrat"],"firstnames":["Anne"],"suffixes":[]},{"propositions":[],"lastnames":["West"],"firstnames":["Jay","A","A"],"suffixes":[]},{"propositions":[],"lastnames":["Panagiotakos"],"firstnames":["Georgia"],"suffixes":[]},{"propositions":[],"lastnames":["Alvarez-Buylla"],"firstnames":["Arturo"],"suffixes":[]},{"propositions":[],"lastnames":["Paredes"],"firstnames":["Mercedes","F"],"suffixes":[]},{"propositions":[],"lastnames":["Nowakowski"],"firstnames":["Tomasz","J"],"suffixes":[]},{"propositions":[],"lastnames":["Pollen"],"firstnames":["Alex","A"],"suffixes":[]},{"propositions":[],"lastnames":["Kriegstein"],"firstnames":["Arnold","R"],"suffixes":[]}],"abstract":"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 Ca(2+) elevations in response to neurotransmitter receptor agonists and RNA sequencing of the same single cells, we show that Ca(2+) 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.","journal":"Neuron","volume":"102","number":"1","pages":"143–158.e7","month":"February","year":"2019","keywords":"calcium imaging; differentiation; human neocortical development; intermediate progenitor cells; neurogenesis; neurotransmitter; radial glia; radial glia scaffold; serotonin; single-cell RNA sequencing","language":"en","bibtex":"@ARTICLE{Mayer2019-tl,\n title = \"Multimodal {Single-Cell} Analysis Reveals Physiological\n Maturation in the Developing Human Neocortex\",\n author = \"Mayer, Simone and Chen, Jiadong and Velmeshev, Dmitry and Mayer,\n Andreas and Eze, Ugomma C and Bhaduri, Aparna and Cunha, Carlos E\n and Jung, Diane and Arjun, Arpana and Li, Emmy and Alvarado,\n Beatriz and Wang, Shaohui and Lovegren, Nils and Gonzales,\n Michael L and Szpankowski, Lukasz and Leyrat, Anne and West, Jay\n A A and Panagiotakos, Georgia and Alvarez-Buylla, Arturo and\n Paredes, Mercedes F and Nowakowski, Tomasz J and Pollen, Alex A\n and Kriegstein, Arnold R\",\n abstract = \"In the developing human neocortex, progenitor cells generate\n diverse cell types prenatally. Progenitor cells and newborn\n neurons respond to signaling cues, including neurotransmitters.\n While single-cell RNA sequencing has revealed cellular diversity,\n physiological heterogeneity has yet to be mapped onto these\n developing and diverse cell types. By combining measurements of\n intracellular Ca(2+) elevations in response to neurotransmitter\n receptor agonists and RNA sequencing of the same single cells, we\n show that Ca(2+) responses are cell-type-specific and change\n dynamically with lineage progression. Physiological response\n properties predict molecular cell identity and additionally\n reveal diversity not captured by single-cell transcriptomics. We\n find that the serotonin receptor HTR2A selectively activates\n radial glia cells in the developing human, but not mouse,\n neocortex, and inhibiting HTR2A receptors in human radial glia\n disrupts the radial glial scaffold. We show highly specific\n neurotransmitter signaling during neurogenesis in the developing\n human neocortex and highlight evolutionarily divergent mechanisms\n of physiological signaling.\",\n journal = \"Neuron\",\n volume = 102,\n number = 1,\n pages = \"143--158.e7\",\n month = feb,\n year = 2019,\n keywords = \"calcium imaging; differentiation; human neocortical development;\n intermediate progenitor cells; neurogenesis; neurotransmitter;\n radial glia; radial glia scaffold; serotonin; single-cell RNA\n sequencing\",\n language = \"en\"\n}\n\n","author_short":["Mayer, S.","Chen, J.","Velmeshev, D.","Mayer, A.","Eze, U. C","Bhaduri, A.","Cunha, C. E","Jung, D.","Arjun, A.","Li, E.","Alvarado, B.","Wang, S.","Lovegren, N.","Gonzales, M. L","Szpankowski, L.","Leyrat, A.","West, J. A A","Panagiotakos, G.","Alvarez-Buylla, A.","Paredes, M. F","Nowakowski, T. J","Pollen, A. A","Kriegstein, A. R"],"key":"Mayer2019-tl","id":"Mayer2019-tl","bibbaseid":"mayer-chen-velmeshev-mayer-eze-bhaduri-cunha-jung-etal-multimodalsinglecellanalysisrevealsphysiologicalmaturationinthedevelopinghumanneocortex-2019","role":"author","urls":{},"keyword":["calcium imaging; differentiation; human neocortical development; intermediate progenitor cells; neurogenesis; neurotransmitter; radial glia; radial glia scaffold; serotonin; single-cell RNA sequencing"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/f/EJMp3HRuxirjxpcXh/references.bib","dataSources":["sAFYeB74DpbdXM9NN","4zx9n2tbeLTix3Wxr","k3cdWrThyTh5o59Rm","hq9pebjzmsTuyxGGx","h8Atv2SAy4PmShg5j"],"keywords":["calcium imaging; differentiation; human neocortical development; intermediate progenitor cells; neurogenesis; neurotransmitter; radial glia; radial glia scaffold; serotonin; single-cell rna sequencing"],"search_terms":["multimodal","single","cell","analysis","reveals","physiological","maturation","developing","human","neocortex","mayer","chen","velmeshev","mayer","eze","bhaduri","cunha","jung","arjun","li","alvarado","wang","lovegren","gonzales","szpankowski","leyrat","west","panagiotakos","alvarez-buylla","paredes","nowakowski","pollen","kriegstein"],"title":"Multimodal Single-Cell Analysis Reveals Physiological Maturation in the Developing Human Neocortex","year":2019}