Human neocortical expansion involves glutamatergic neuron diversification

被引：163

作者：

Berg, Jim ^{[1
]}

Sorensen, Staci A. ^{[1
]}

Ting, Jonathan T. ^{[1
,2
]}

Miller, Jeremy A. ^{[1
]}

Chartrand, Thomas ^{[1
]}

Buchin, Anatoly ^{[1
]}

Bakken, Trygve E. ^{[1
]}

Budzillo, Agata ^{[1
]}

Dee, Nick ^{[1
]}

Ding, Song-Lin ^{[1
]}

Gouwens, Nathan W. ^{[1
]}

Hodge, Rebecca D. ^{[1
]}

Kalmbach, Brian ^{[1
,2
]}

Lee, Changkyu ^{[1
]}

Lee, Brian R. ^{[1
]}

Alfiler, Lauren ^{[1
]}

Baker, Katherine ^{[1
]}

Barkan, Eliza ^{[1
]}

Beller, Allison ^{[3
]}

Berry, Kyla ^{[1
]}

Bertagnolli, Darren ^{[1
]}

Bickley, Kris ^{[1
]}

Bomben, Jasmine ^{[1
]}

Braun, Thomas ^{[4
]}

Brouner, Krissy ^{[1
]}

Casper, Tamara ^{[1
]}

Chong, Peter ^{[1
]}

Crichton, Kirsten ^{[1
]}

Dalley, Rachel ^{[1
]}

de Frates, Rebecca ^{[1
]}

Desta, Tsega ^{[1
]}

Lee, Samuel Dingman ^{[1
]}

D'Orazi, Florence ^{[1
]}

Dotson, Nadezhda ^{[1
]}

Egdorf, Tom ^{[1
]}

Enstrom, Rachel ^{[1
]}

Farrell, Colin ^{[1
]}

Feng, David ^{[1
]}

Fong, Olivia ^{[1
]}

Furdan, Szabina ^{[5
]}

Galakhova, Anna A. ^{[6
]}

Gamlin, Clare ^{[1
]}

Gary, Amanda ^{[1
]}

Glandon, Alexandra ^{[1
]}

Goldy, Jeff ^{[1
]}

Gorham, Melissa ^{[1
]}

Goriounova, Natalia A. ^{[6
]}

Gratiy, Sergey ^{[1
]}

Graybuck, Lucas ^{[1
]}

Gu, Hong ^{[1
]}

机构：

[1] Allen Inst Brain Sci, Seattle, WA 98109 USA

[2] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA

[3] Univ Washington, Dept Pathol, Seattle, WA 98195 USA

[4] Byte Phys, Berlin, Germany

[5] Univ Szeged, MTA SZTE Res Grp Cort Microcircuits, Dept Physiol Anat & Neurosci, Szeged, Hungary

[6] Vrije Univ, Ctr Neurogen & Cognit Res CNCR, Dept Integrat Neurophysiol, Amsterdam, Netherlands

[7] Swedish Neurosci Inst, Seattle, WA USA

[8] Univ Szeged, Dept Neurosurg, Szeged, Hungary

[9] Vrije Univ, Canc Ctr Amsterdam, Brain Tumor Ctr, Dept Neurosurg,Amsterdam UMC, Amsterdam, Netherlands

[10] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA

[11] Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, New York, NY 10029 USA

[12] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA

[13] Columbia Univ, NeuroTechnol Ctr, New York, NY USA

[14] Hebrew Univ Jerusalem, Edmond & Lily Safra Ctr Brain Sci, Jerusalem, Israel

[15] Hebrew Univ Jerusalem, Dept Neurobiol, Jerusalem, Israel

来源：

NATURE | 2021年 / 598卷 / 7879期

基金：

美国国家卫生研究院;

关键词：

PYRAMIDAL NEURONS; QUANTITATIVE-ANALYSIS; PREFRONTAL CORTEX; PROJECTION NEURONS; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; MACAQUE MONKEY; CELL-TYPES; RNA-SEQ; VISUALIZATION;

D O I：

10.1038/s41586-021-03813-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The neocortex is disproportionately expanded in human compared with mouse(1,2), both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth(3). Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues. We demonstrate a strong correspondence between morphological, physiological and transcriptomic phenotypes of five human glutamatergic supragranular neuron types. These were enriched in but not restricted to layers, with one type varying continuously in all phenotypes across layers 2 and 3. The deep portion of layer 3 contained highly distinctive cell types, two of which express a neurofilament protein that labels long-range projection neurons in primates that are selectively depleted in Alzheimer's disease(4,5). Together, these results demonstrate the explanatory power of transcriptomic cell-type classification, provide a structural underpinning for increased complexity of cortical function in humans, and implicate discrete transcriptomic neuron types as selectively vulnerable in disease.

引用

页码：151 / +

页数：29

共 70 条

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