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研究揭示小鼠小脑细胞中顺式调控元件的发育和进化动态
作者:小柯机器人 发布时间:2021/7/31 23:14:23

德国海德堡大学Henrik Kaessmann等研究人员合作揭示小鼠小脑细胞中顺式调控元件的发育和进化动态。相关论文于2021年7月29日在线发表在《科学》杂志上。

研究人员调查了小鼠小脑发育从早期神经发生到成年的调节基础。通过获取跨越11个阶段的约90,000个细胞的snATAC-seq图谱,研究人员绘制了小脑细胞类型并确定了候选顺式调控元件(CRE)。研究人员检测到祖细胞之间广泛的时空异质性,以及小脑神经元在分化过程中调节程序的逐渐分化。

与脊椎动物基因组和负鼠20,000个小脑细胞的snATAC-seq图谱进行比较,研究人员发现在发育和分化过程中,CRE的保守程度共同下降,并且细胞类型之间的限制也有差异。这项工作划定了小脑细胞中基因调控的发展和进化动态,并提供了对哺乳动物器官发育的见解。

据了解,器官的发育是由细胞和时间特定的基因调控网络来安排的。

附:英文原文

Title: Developmental and evolutionary dynamics of cis-regulatory elements in mouse cerebellar cells

Author: Ioannis Sarropoulos, Mari Sepp, Robert Frmel, Kevin Leiss, Nils Trost, Evgeny Leushkin, Konstantin Okonechnikov, Piyush Joshi, Peter Giere, Lena M. Kutscher, Margarida Cardoso-Moreira, Stefan M. Pfister, Henrik Kaessmann

Issue&Volume: 2021/07/29

Abstract: Organ development is orchestrated by cell- and time-specific gene regulatory networks. In this study, we investigated the regulatory basis of mouse cerebellum development from early neurogenesis to adulthood. By acquiring snATAC-seq profiles for ~90,000 cells spanning eleven stages, we mapped cerebellar cell types and identified candidate cis-regulatory elements (CREs). We detected extensive spatiotemporal heterogeneity among progenitor cells and a gradual divergence in the regulatory programs of cerebellar neurons during differentiation. Comparisons to vertebrate genomes and snATAC-seq profiles for ~20,000 cerebellar cells from the marsupial opossum revealed a shared decrease in CRE conservation during development and differentiation, but also differences in constraint between cell types. Our work delineates the developmental and evolutionary dynamics of gene regulation in cerebellar cells and provides insights into mammalian organ development.

DOI: 10.1126/science.abg4696

Source: https://science.sciencemag.org/content/early/2021/07/28/science.abg4696

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037