Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map

被引：324

作者：

Bayraktar, Omer Ali ^{[1
,2
,3
,4
]}

Bartels, Theresa ^{[1
]}

Holmqvist, Staffan ^{[1
]}

Kleshchevnikov, Vitalii ^{[4
]}

Martirosyan, Araks ^{[5
]}

Polioudakis, Damon ^{[6
,7
,8
]}

Ben Haim, Lucile ^{[1
]}

Young, Adam M. H. ^{[9
]}

Batiuk, Mykhailo Y. ^{[5
]}

Prakash, Kirti ^{[1
]}

Brown, Alexander ^{[10
]}

Roberts, Kenny ^{[4
]}

Paredes, Mercedes F. ^{[2
,3
,11
]}

Kawaguchi, Riki ^{[12
]}

Stockley, John H. ^{[1
]}

Sabeur, Khalida ^{[1
,2
,3
]}

Chang, Sandra M. ^{[1
,2
,3
]}

Huang, Eric ^{[11
,13
]}

Hutchinson, Peter ^{[9
]}

Ullian, Erik M. ^{[14
]}

Hemberg, Martin ^{[4
]}

Coppola, Giovanni ^{[6
,7
,12
]}

Holt, Matthew G. ^{[5
]}

Geschwind, Daniel H. ^{[6
,7
,8
]}

Rowitch, David H. ^{[1
,2
,3
]}

机构：

[1] Univ Cambridge, Wellcome MRC Cambridge Stem Cell Inst, Dept Paediat, Cambridge, England

[2] Univ Calif San Francisco, Dept Pediat, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94115 USA

[3] Univ Calif San Francisco, Dept Neurosurg, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94115 USA

[4] Wellcome Sanger Inst, Hinxton, England

[5] Katholieke Univ Leuven, VIB KU Leuven Ctr Brain & Dis Res, Lab Glia Biol, Dept Neurosci, Leuven, Belgium

[6] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA

[7] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA

[8] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Ctr Autism Res & Treatment, Los Angeles, CA 90095 USA

[9] Univ Cambridge, Div Acad Neurosurg, Dept Clin Neurosci, Cambridge, England

[10] UCL, Sainsbury Wellcome Ctr, London, England

[11] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA

[12] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA

[13] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA

[14] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA

来源：

NATURE NEUROSCIENCE | 2020年 / 23卷 / 04期

基金：

英国惠康基金; 美国国家卫生研究院; 英国医学研究理事会; 欧洲研究理事会;

关键词：

PROJECTION NEURON IDENTITY; SATB2; GLIA; HYBRIDIZATION; PROTEINS; CALLOSAL;

D O I：

10.1038/s41593-020-0602-1

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Although the cerebral cortex is organized into six excitatory neuronal layers, it is unclear whether glial cells show distinct layering. In the present study, we developed a high-content pipeline, the large-area spatial transcriptomic (LaST) map, which can quantify single-cell gene expression in situ. Screening 46 candidate genes for astrocyte diversity across the mouse cortex, we identified superficial, mid and deep astrocyte identities in gradient layer patterns that were distinct from those of neurons. Astrocyte layer features, established in the early postnatal cortex, mostly persisted in adult mouse and human cortex. Single-cell RNA sequencing and spatial reconstruction analysis further confirmed the presence of astrocyte layers in the adult cortex. Satb2 and Reeler mutations that shifted neuronal post-mitotic development were sufficient to alter glial layering, indicating an instructive role for neuronal cues. Finally, astrocyte layer patterns diverged between mouse cortical regions. These findings indicate that excitatory neurons and astrocytes are organized into distinct lineage-associated laminae. A new spatial transcriptomic approach reveals astrocyte heterogeneity across layers of the mammalian cerebral cortex. Astrocytes diversify into superficial-, mid- and deep-layer subtypes distinct from neuronal laminae, yet instructed by neuronal cues.

引用

页码：500 / +

页数：14

共 47 条

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Satb2 regulates callosal projection neuron identity in the developing cerebral cortex [J].