Collaborative Research: URoL: Epigenetics 2: Epigenetics in development and Evolution of Primate Brains

合作研究：URoL：表观遗传学 2：灵长类动物大脑发育和进化中的表观遗传学

• 批准号: 2021785
• 负责人: Chet Sherwood
• 金额: $ 45.88万
• 依托单位: George Washington University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2021785&HistoricalAwards=false
• 关键词: Collaborative; Research; URoL; Epigenetics; development

The proposed research will examine naturally occurring molecular variation in the brains of humans and other primates to understand how modifications to the function of genes in the brain relate to differences in developmental and social experience across species. The proposal is highly interdisciplinary, incorporating methods and perspectives from molecular biology, anthropology, neuroscience and psychology, and will advance fundamental knowledge about mechanistic processes underlying gene-environment interactions in the brains of highly social species. In addition to offering interdisciplinary training for graduate and undergraduate students during the proposed research, the PIs will integrate research opportunities with outreach efforts for high school students, high school teachers, and also for broader public audiences, including children. Comparative studies of primates offer great educational and outreach potential due to their deep implications for understanding humans’ place in nature. Furthermore, the brain is the most widely studied organ in genetic and psychological studies, making the datasets this project will generate especially worthwhile as open resources for the scientific community. All research conducted will be published in peer-reviewed scientific journals and disseminated in scientific meetings. Nonhuman primates have been important model species for the study of mechanisms underlying the biological, genetic and neural basis of a variety of behavioral and cognitive functions. Many aspects of primate brains, including size, structural variation and rate of maturation are tightly associated with life history traits such as cognition, gestation length and life span. These differences are also associated with different developmental rates of primate brains. For example, human brains are extremely immature at birth, followed by slow development, providing ample opportunities for interaction between genome and environment to occur. This research project aims to study the molecular record of such genome-environment interaction in the context of primate brain development. Specifically, the investigators will examine DNA methylation, which functions as cellular memory of environmental input and thus moderates genome-environment interactions, and hypothesize that natural variation in brain size and development of primate species will be reflected in variation of DNA methylation, and in turn, gene expression. Several primate species will be included, encompassing naturally occurring variation in life history traits and brain size. Neocortical areas with distinctive developmental patterns, at cellular resolution, will be compared. In addition to phylogenetic variation, the research will utilize a unique opportunity to investigate how early social experiences have shaped DNA methylation and gene expression within species, using archived samples from chimpanzees and baboon colonies. The proposed research will generate novel opportunities to correlate molecular data with brain and cognitive phenotypes across multiple scales of biology.This project is funded by the Understanding the Rules of Life: Epigenetics Program, administered as part of NSF's Ten Big Ideas through the Division of Emerging Frontiers in the Directorate for Biological Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

拟议中的研究将检查人类和其他灵长类动物大脑中自然发生的分子变异，以了解大脑中基因功能的修改如何与物种之间的发育和社会经验差异相关。该提案是高度跨学科的，结合了分子生物学，人类学，神经科学和心理学的方法和观点，并将推进关于高度社会性物种大脑中基因-环境相互作用机制过程的基础知识。除了在拟议的研究期间为研究生和本科生提供跨学科培训外，pi还将把研究机会与面向高中生、高中教师以及包括儿童在内的更广泛公众的推广工作结合起来。灵长类动物的比较研究提供了巨大的教育和推广潜力，因为它们对理解人类在自然界中的地位有着深刻的意义。此外，大脑是遗传和心理学研究中研究最广泛的器官，因此该项目将产生的数据集作为科学界的开放资源特别有价值。所有进行的研究将在同行评议的科学期刊上发表，并在科学会议上传播。非人类灵长类动物已成为研究各种行为和认知功能的生物学、遗传和神经基础机制的重要模式物种。灵长类动物大脑的许多方面，包括大小、结构变异和成熟速度，都与认知、妊娠期和寿命等生活史特征密切相关。这些差异也与灵长类动物大脑的不同发育速度有关。例如，人类大脑在出生时非常不成熟，随后发育缓慢，为基因组和环境之间的相互作用提供了充足的机会。本研究项目旨在研究灵长类动物大脑发育过程中基因组-环境相互作用的分子记录。具体来说，研究人员将研究DNA甲基化，它作为环境输入的细胞记忆，从而调节基因组与环境的相互作用，并假设灵长类物种的大脑大小和发育的自然变化将反映在DNA甲基化的变化中，进而反映在基因表达上。几个灵长类物种将被包括在内，包括生活史特征和大脑大小的自然变异。在细胞分辨率下，将比较具有独特发育模式的新皮质区域。除了系统发育变异之外，这项研究还将利用一个独特的机会，利用黑猩猩和狒狒群体的存档样本，调查早期的社会经历如何影响物种内的DNA甲基化和基因表达。拟议的研究将产生新的机会，在多个生物学尺度上将分子数据与大脑和认知表型相关联。该项目由理解生命规则：表观遗传学项目资助，该项目由生物科学理事会新兴前沿部门管理，是NSF十大理念的一部分。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Chimpanzee Extraversion scores vary with epigenetic modification of dopamine receptor gene D2 ( DRD2 ) and early rearing conditions

黑猩猩的外向性得分随多巴胺受体基因D2（DRD2）的表观遗传修饰和早期饲养条件而变化。

• DOI: 10.1080/15592294.2022.2058224
• 发表时间: 2022
• 期刊: Epigenetics
• 影响因子: 3.7
• 作者: Staes, Nicky;White, Cassandra M.;Guevara, Elaine E;Eens, Marcel;Hopkins, William D.;Schapiro, Steven J.;Stevens, Jeroen M.G.;Sherwood, Chet C.;Bradley, Brenda J
• 通讯作者: Bradley, Brenda J

Epigenetic ageing of the prefrontal cortex and cerebellum in humans and chimpanzees

• DOI: 10.1080/15592294.2022.2080993
• 发表时间: 2022-05
• 期刊: Epigenetics
• 影响因子: 3.7
• 作者: E. E. Guevara-E.;W. Hopkins;P. Hof;J. Ely;B. Bradley;C. Sherwood

Molecular features driving cellular complexity of human brain evolution

• DOI: 10.1038/s41586-023-06338-4
• 发表时间: 2023-07-19
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Caglayan, Emre;Ayhan, Fatma;Konopka, Genevieve
• 通讯作者: Konopka, Genevieve

Molecular and cellular evolution of the primate dorsolateral prefrontal cortex.

• DOI: 10.1126/science.abo7257
• 发表时间: 2022-09-30
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Ma, Shaojie;Skarica, Mario;Li, Qian;Xu, Chuan;Risgaard, Ryan D.;Tebbenkamp, Andrew T. N.;Mato-Blanco, Xoel;Kovner, Rothem;Krsnik, Zeljka;de Martin, Xabier;Luria, Victor;Marti-Perez, Xavier;Liang, Dan;Karger, Amir;Schmidt, Danielle K.;Gomez-Sanchez, Zachary;Qi, Cai;Gobeske, Kevin T.;Pochareddy, Sirisha;Debnath, Ashwin;Hottman, Cade J.;Spurrier, Joshua;Teo, Leon;Boghdadi, Anthony G.;Homman-Ludiye, Jihane;Ely, John J.;Daadi, Etienne W.;Mi, Da;Daadi, Marcel;Marin, Oscar;Hof, Patrick R.;Rasin, Mladen-Roko;Bourne, James;Sherwood, Chet C.;Santpere, Gabriel;Girgenti, Matthew J.;Strittmatter, Stephen M.;Sousa, Andre M. M.;Sestan, Nenad
• 通讯作者: Sestan, Nenad

The nucleus accumbens and ventral pallidum exhibit greater dopaminergic innervation in humans compared to other primates

与其他灵长类动物相比，人类的伏隔核和腹侧苍白球表现出更强的多巴胺能神经支配

• DOI: 10.1007/s00429-021-02300-0
• 发表时间: 2021
• 期刊: Brain Structure and Function
• 影响因子: 3.1
• 作者: Hirter, Kristen N.;Miller, Elaine N.;Stimpson, Cheryl D.;Phillips, Kimberley A.;Hopkins, William D.;Hof, Patrick R.;Sherwood, Chet C.;Lovejoy, C. Owen;Raghanti, Mary Ann
• 通讯作者: Raghanti, Mary Ann