Human neocortical expansion involves glutamatergic neuron diversification.
Human neocortical expansion involves glutamatergic neuron diversification.
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人类新皮质扩张涉及谷氨酸能神经元多样化。
DOI：
10.1038/s41586-021-03813-8
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发表时间：
2021-10
期刊：
影响因子：
64.8
通讯作者：
Lein ES
中科院分区：
文献类型：
--
作者：
Berg J;Sorensen SA;Ting JT;Miller JA;Chartrand T;Buchin A;Bakken TE;Budzillo A;Dee N;Ding SL;Gouwens NW;Hodge RD;Kalmbach B;Lee C;Lee BR;Alfiler L;Baker K;Barkan E;Beller A;Berry K;Bertagnolli D;Bickley K;Bomben J;Braun T;Brouner K;Casper T;Chong P;Crichton K;Dalley R;de Frates R;Desta T;Lee SD;D'Orazi F;Dotson N;Egdorf T;Enstrom R;Farrell C;Feng D;Fong O;Furdan S;Galakhova AA;Gamlin C;Gary A;Glandon A;Goldy J;Gorham M;Goriounova NA;Gratiy S;Graybuck L;Gu H;Hadley K;Hansen N;Heistek TS;Henry AM;Heyer DB;Hill D;Hill C;Hupp M;Jarsky T;Kebede S;Keene L;Kim L;Kim MH;Kroll M;Latimer C;Levi BP;Link KE;Mallory M;Mann R;Marshall D;Maxwell M;McGraw M;McMillen D;Melief E;Mertens EJ;Mezei L;Mihut N;Mok S;Molnar G;Mukora A;Ng L;Ngo K;Nicovich PR;Nyhus J;Olah G;Oldre A;Omstead V;Ozsvar A;Park D;Peng H;Pham T;Pom CA;Potekhina L;Rajanbabu R;Ransford S;Reid D;Rimorin C;Ruiz A;Sandman D;Sulc J;Sunkin SM;Szafer A;Szemenyei V;Thomsen ER;Tieu M;Torkelson A;Trinh J;Tung H;Wakeman W;Waleboer F;Ward K;Wilbers R;Williams G;Yao Z;Yoon JG;Anastassiou C;Arkhipov A;Barzo P;Bernard A;Cobbs C;de Witt Hamer PC;Ellenbogen RG;Esposito L;Ferreira M;Gwinn RP;Hawrylycz MJ;Hof PR;Idema S;Jones AR;Keene CD;Ko AL;Murphy GJ;Ng L;Ojemann JG;Patel AP;Phillips JW;Silbergeld DL;Smith K;Tasic B;Yuste R;Segev I;de Kock CPJ;Mansvelder HD;Tamas G;Zeng H;Koch C;Lein ES
与小鼠相比，人类的新皮质不成比例地扩大，无论是在其相对于皮质下结构的总体积还是在由选择性地在新皮质内与其他端脑结构建立连接的神经元组成的颗粒上层所占据的比例上。人类和小鼠新皮质的单细胞转录组学分析显示，在人类新皮质的颗粒上层中的神经元类型的多样性增加，并且作为皮质深度的函数的梯度明显。在这里，为了探索这种转录组多样性的功能和解剖学相关性，我们开发了一个强大的平台，结合膜片钳记录，生物胞素染色和单细胞RNA测序（Patch-seq）来检查神经外科切除的人体组织。我们证明了一个强大的对应关系之间的形态，生理和转录组表型的五个人类mammatergic颗粒上神经元类型。这些在层中富集但不限于层，其中一种类型在第2层和第3层的所有表型中连续变化。第3层的深部含有高度独特的细胞类型，其中两种表达一种神经丝蛋白，该蛋白标记在阿尔茨海默病中选择性耗尽的灵长类动物中的长程投射神经元。总之，这些结果证明了转录组细胞类型分类的解释能力，为人类皮质功能的复杂性增加提供了结构基础，并暗示离散的转录组神经元类型在疾病中选择性脆弱。人神经皮层神经元的组合膜片钳记录、生物胞素染色和单细胞RNA测序显示出相对于小鼠的多巴胺能神经元类型的扩展，其表征了人新皮层的更大复杂性。
The neocortex is disproportionately expanded in human compared with mouse, 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. 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. 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. Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.
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影响因子：
46.9
作者：
Fuzik J;Zeisel A;Máté Z;Calvigioni D;Yanagawa Y;Szabó G;Linnarsson S;Harkany T
通讯作者：
Harkany T
影响因子：
46.9
作者：
Cadwell CR;Palasantza A;Jiang X;Berens P;Deng Q;Yilmaz M;Reimer J;Shen S;Bethge M;Tolias KF;Sandberg R;Tolias AS
通讯作者：
Tolias AS
影响因子：
5.3
作者：
Calcagnotto, ME;Paredes, MF;Baraban, SC
通讯作者：
Baraban, SC
影响因子：
64.5
作者：
Gouwens NW;Sorensen SA;Baftizadeh F;Budzillo A;Lee BR;Jarsky T;Alfiler L;Baker K;Barkan E;Berry K;Bertagnolli D;Bickley K;Bomben J;Braun T;Brouner K;Casper T;Crichton K;Daigle TL;Dalley R;de Frates RA;Dee N;Desta T;Lee SD;Dotson N;Egdorf T;Ellingwood L;Enstrom R;Esposito L;Farrell C;Feng D;Fong O;Gala R;Gamlin C;Gary A;Glandon A;Goldy J;Gorham M;Graybuck L;Gu H;Hadley K;Hawrylycz MJ;Henry AM;Hill D;Hupp M;Kebede S;Kim TK;Kim L;Kroll M;Lee C;Link KE;Mallory M;Mann R;Maxwell M;McGraw M;McMillen D;Mukora A;Ng L;Ng L;Ngo K;Nicovich PR;Oldre A;Park D;Peng H;Penn O;Pham T;Pom A;Popović Z;Potekhina L;Rajanbabu R;Ransford S;Reid D;Rimorin C;Robertson M;Ronellenfitch K;Ruiz A;Sandman D;Smith K;Sulc J;Sunkin SM;Szafer A;Tieu M;Torkelson A;Trinh J;Tung H;Wakeman W;Ward K;Williams G;Zhou Z;Ting JT;Arkhipov A;Sümbül U;Lein ES;Koch C;Yao Z;Tasic B;Berg J;Murphy GJ;Zeng H
通讯作者：
Zeng H
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG