A comprehensive transcriptional map of primate brain development.
A comprehensive transcriptional map of primate brain development.
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DOI：
10.1038/nature18637
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发表时间：
2016-07-21
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：
Bakken TE;Miller JA;Ding SL;Sunkin SM;Smith KA;Ng L;Szafer A;Dalley RA;Royall JJ;Lemon T;Shapouri S;Aiona K;Arnold J;Bennett JL;Bertagnolli D;Bickley K;Boe A;Brouner K;Butler S;Byrnes E;Caldejon S;Carey A;Cate S;Chapin M;Chen J;Dee N;Desta T;Dolbeare TA;Dotson N;Ebbert A;Fulfs E;Gee G;Gilbert TL;Goldy J;Gourley L;Gregor B;Gu G;Hall J;Haradon Z;Haynor DR;Hejazinia N;Hoerder-Suabedissen A;Howard R;Jochim J;Kinnunen M;Kriedberg A;Kuan CL;Lau C;Lee CK;Lee F;Luong L;Mastan N;May R;Melchor J;Mosqueda N;Mott E;Ngo K;Nyhus J;Oldre A;Olson E;Parente J;Parker PD;Parry S;Pendergraft J;Potekhina L;Reding M;Riley ZL;Roberts T;Rogers B;Roll K;Rosen D;Sandman D;Sarreal M;Shapovalova N;Shi S;Sjoquist N;Sodt AJ;Townsend R;Velasquez L;Wagley U;Wakeman WB;White C;Bennett C;Wu J;Young R;Youngstrom BL;Wohnoutka P;Gibbs RA;Rogers J;Hohmann JG;Hawrylycz MJ;Hevner RF;Molnár Z;Phillips JW;Dang C;Jones AR;Amaral DG;Bernard A;Lein ES
大脑发育的转录基础仍然知之甚少，特别是在人类和密切相关的非人类灵长类动物中。我们描述了一个高分辨率的恒河猴大脑发育的转录图谱，结合了密集的时间采样的产前和产后时期与人类神经精神疾病相关的皮质和皮质下区域的精细解剖parcellation。出生前，祖细胞和成熟神经元中的基因表达变化更快，皮质层和区域在出生后很晚才获得类似成人的分子谱。不同的细胞群体表现出不同的发育时间，但也意想不到的同步过程的神经回路的建设，包括细胞的投影和粘附。神经发育障碍包括原发性小头畸形、自闭症谱系障碍、智力残疾和精神分裂症的候选风险基因在发育中的新皮层中显示出疾病特异性时空富集。人类发育的表达轨迹更类似于猴子而不是啮齿动物，大约9%的基因显示出人类特异性调控，并有证据表明成熟或幼态持续延长。
The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high resolution transcriptional atlas of rhesus monkey brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical parcellation of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons, and cortical layers and areas acquire adult-like molecular profiles surprisingly late postnatally. Disparate cell populations exhibit distinct developmental timing but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, and approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny.