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全基因组表达谱分析揭示了小鼠和人类胚胎发育差异背后的遗传程序。

Global expression profiling reveals genetic programs underlying the developmental divergence between mouse and human embryogenesis.

作者信息

Xue Lu, Cai Jin-Yang, Ma Jian, Huang Zan, Guo Ming-Xiong, Fu Lie-Zhen, Shi Yun-Bo, Li Wen-Xin

机构信息

College of Life Sciences, Wuhan University, Wuhan 430072, P,R China.

出版信息

BMC Genomics. 2013 Aug 20;14:568. doi: 10.1186/1471-2164-14-568.

Abstract

BACKGROUND

Mouse has served as an excellent model for studying human development and diseases due to its similarity to human. Advances in transgenic and knockout studies in mouse have dramatically strengthened the use of this model and significantly improved our understanding of gene function during development in the past few decades. More recently, global gene expression analyses have revealed novel features in early embryogenesis up to gastrulation stages and have indeed provided molecular evidence supporting the conservation in early development in human and mouse. On the other hand, little information is known about the gene regulatory networks governing the subsequent organogenesis. Importantly, mouse and human development diverges during organogenesis. For instance, the mouse embryo is born around the end of organogenesis while in human the subsequent fetal period of ongoing growth and maturation of most organs spans more than 2/3 of human embryogenesis. While two recent studies reported the gene expression profiles during human organogenesis, no global gene expression analysis had been done for mouse organogenesis.

RESULTS

Here we report a detailed analysis of the global gene expression profiles from egg to the end of organogenesis in mouse. Our studies have revealed distinct temporal regulation patterns for genes belonging to different functional (Gene Ontology or GO) categories that support their roles during organogenesis. More importantly, comparative analyses identify both conserved and divergent gene regulation programs in mouse and human organogenesis, with the latter likely responsible for the developmental divergence between the two species, and further suggest a novel developmental strategy during vertebrate evolution.

CONCLUSIONS

We have reported here the first genome-wide gene expression analysis of the entire mouse embryogenesis and compared the transcriptome atlas during mouse and human embryogenesis. Given our earlier observation that genes function in a given process tends to be developmentally co-regulated during organogenesis, our microarray data here should help to identify genes associated with mouse development and/or infer the developmental functions of unknown genes. In addition, our study might be useful for invesgtigating the molecular basis of vertebrate evolution.

摘要

背景

由于小鼠与人类的相似性,它一直是研究人类发育和疾病的优秀模型。在过去几十年中,小鼠转基因和基因敲除研究的进展极大地加强了该模型的应用,并显著增进了我们对发育过程中基因功能的理解。最近,全基因组基因表达分析揭示了从早期胚胎发生到原肠胚形成阶段的新特征,并确实提供了支持人类和小鼠早期发育保守性的分子证据。另一方面,关于控制随后器官发生的基因调控网络,我们所知甚少。重要的是,小鼠和人类的发育在器官发生过程中出现分歧。例如,小鼠胚胎在器官发生末期出生,而在人类中,大多数器官持续生长和成熟的后续胎儿期跨越了人类胚胎发生的2/3以上时间。虽然最近有两项研究报道了人类器官发生过程中的基因表达谱,但尚未对小鼠器官发生进行全基因组基因表达分析。

结果

在此,我们报告了对小鼠从卵子到器官发生末期的全基因组基因表达谱的详细分析。我们的研究揭示了属于不同功能(基因本体论或GO)类别的基因具有独特的时间调控模式,这支持了它们在器官发生过程中的作用。更重要的是,比较分析确定了小鼠和人类器官发生中保守和不同的基因调控程序,后者可能是这两个物种发育差异的原因,并进一步提示了脊椎动物进化过程中的一种新的发育策略。

结论

我们在此报告了首次对整个小鼠胚胎发生进行的全基因组基因表达分析,并比较了小鼠和人类胚胎发生过程中的转录组图谱。鉴于我们早期的观察结果,即在器官发生过程中,在给定过程中起作用的基因往往在发育上共同调控,我们这里所提供的微阵列数据应有助于识别与小鼠发育相关的基因和/或推断未知基因的发育功能。此外,我们的研究可能有助于探究脊椎动物进化的分子基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d1/3924405/169971d29fd4/1471-2164-14-568-1.jpg

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