德国海德堡大学Henrik Kaessmann等研究人员合作揭示哺乳动物小脑的细胞发育和演化。这一研究成果于2023年11月29日在线发表在国际学术期刊《自然》上。

研究人员生成了约40万个细胞的单核RNA测序数据，以追踪人、小鼠和有袋类负鼠从早期神经发生到成年期的小脑发育过程。研究人员建立了哺乳动物小脑发育过程中细胞多样性的共识分类，并通过在胎儿期人类小脑中绘制空间图进行了验证。跨物种分析揭示了细胞类型生成的基本一致的发育动态，除了Purkinje细胞，研究人员观察到人类谱系中早期亚型的扩大。全局转录组图谱、保守的细胞状态标记和跨神经元分化的基因表达轨迹表明，小脑细胞类型定义程序总体上至少保存了约1.6亿年。

不过，研究人员也发现了许多同源基因，这些基因在其中一个物种的小脑神经细胞类型中获得或失去表达，或者在神经元分化过程中演化出新的表达轨迹，这表明在细胞类型水平存在广泛的基因再利用现象。总之，这项研究揭示了支配小脑细胞发育的共享基因表达程序和特定谱系基因表达程序，并拓展了人们对哺乳动物大脑演化的理解。

据了解，新皮层的扩张是哺乳动物演化的标志，与此同时，小脑神经元的数量也在增加。然而，人们对哺乳动物小脑发育所依赖的细胞程序的演化知之甚少。

附：英文原文

Title: Cellular development and evolution of the mammalian cerebellum

Author: Sepp, Mari, Leiss, Kevin, Murat, Florent, Okonechnikov, Konstantin, Joshi, Piyush, Leushkin, Evgeny, Spnig, Lisa, Mbengue, Noe, Schneider, Cline, Schmidt, Julia, Trost, Nils, Schauer, Maria, Khaitovich, Philipp, Lisgo, Steven, Palkovits, Mikls, Giere, Peter, Kutscher, Lena M., Anders, Simon, Cardoso-Moreira, Margarida, Sarropoulos, Ioannis, Pfister, Stefan M., Kaessmann, Henrik

Issue&Volume: 2023-11-29

Abstract: The expansion of the neocortex, a hallmark of mammalian evolution1,2, was accompanied by an increase in cerebellar neuron numbers3. However, little is known about the evolution of the cellular programs underlying cerebellum development in mammals. In this study, we generated single-nucleus RNA-sequencing data for ~400,000 cells to trace cerebellum development from early neurogenesis to adulthood in human, mouse, and the marsupial opossum. We established a consensus classification of the cellular diversity in the developing mammalian cerebellum and validated it by spatial mapping in the fetal human cerebellum. Our cross-species analyses revealed a largely conserved developmental dynamics of cell type generation, except for Purkinje cells, where we observed an expansion of early-born subtypes in the human lineage. Global transcriptome profiles, conserved cell state markers, and gene expression trajectories across neuronal differentiation show that cerebellar cell type-defining programs have been overall preserved for at least ~160 million years. However, we also identified many orthologous genes that gained or lost expression in cerebellar neural cell types in one of the species, or evolved new expression trajectories during neuronal differentiation, indicating widespread gene repurposing at the cell type level. Altogether, our study unveils shared and lineage-specific gene expression programs governing the development of cerebellar cells, and expands our understanding of mammalian brain evolution.

DOI: 10.1038/s41586-023-06884-x

Source: https://www.nature.com/articles/s41586-023-06884-x

期刊信息

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504

官方网址：http://www.nature.com

投稿链接：http://www.nature.com/authors/submit_manuscript.html