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胚胎干细胞和小鼠胚胎中原肌球蛋白基因表达的发育分析。

Developmental analysis of tropomyosin gene expression in embryonic stem cells and mouse embryos.

作者信息

Muthuchamy M, Pajak L, Howles P, Doetschman T, Wieczorek D F

机构信息

Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Ohio 45267-0524.

出版信息

Mol Cell Biol. 1993 Jun;13(6):3311-23. doi: 10.1128/mcb.13.6.3311-3323.1993.

Abstract

Tropomyosins (TMs) comprise a family of actin-binding proteins which play an important role in the regulation of contractility in muscle (cardiac, skeletal, and smooth) and nonmuscle cells. Although they are present in all cells, different isoforms are characteristic of specific cell types. In vertebrates, there are four different TM genes (alpha-TM, beta-TM, TM30, and TM4), three of which generate alternatively spliced isoforms. This study defines the expression patterns of these isoforms during murine embryogenesis, using both in vivo and in vitro conditions. The embryonic stem cell culture system, which has been shown to mimic different stages of mouse embryonic development, including the differentiation of primitive organ systems such as the myocardium, is used for our in vitro analysis. Our results demonstrate that several TM isoforms are expressed in specific developmental patterns, often correlated with the differentiation of particular tissues or organs. Surprisingly, other TMs, such as the striated muscle beta-TM and smooth muscle alpha-TM, are expressed constitutively. This study also demonstrates that there is an excellent correlation between the expression patterns of the TM isoforms observed in developing embryonic stem cells and mouse embryos. In addition, a quantitative molecular analysis of TM isoforms was conducted in embryonic, neonatal, and adult cardiac tissue. Our results show for the first time that the alpha- and beta-TM striated muscle transcripts are present in the earliest functional stages of the heart, and these TM isoforms are identical to those present throughout cardiac development.

摘要

原肌球蛋白(TMs)是一类肌动蛋白结合蛋白家族,在肌肉(心肌、骨骼肌和平滑肌)和非肌肉细胞的收缩调节中发挥重要作用。尽管它们存在于所有细胞中,但不同的同工型是特定细胞类型所特有的。在脊椎动物中,有四种不同的TM基因(α-TM、β-TM、TM30和TM4),其中三种产生可变剪接的同工型。本研究利用体内和体外条件定义了这些同工型在小鼠胚胎发育过程中的表达模式。胚胎干细胞培养系统已被证明可模拟小鼠胚胎发育的不同阶段,包括原始器官系统如心肌的分化,用于我们的体外分析。我们的结果表明,几种TM同工型以特定的发育模式表达,通常与特定组织或器官的分化相关。令人惊讶的是,其他TMs,如横纹肌β-TM和平滑肌α-TM,是组成性表达的。本研究还表明,在发育中的胚胎干细胞和小鼠胚胎中观察到的TM同工型的表达模式之间存在极好的相关性。此外,对胚胎、新生儿和成年心脏组织中的TM同工型进行了定量分子分析。我们的结果首次表明,α-和β-TM横纹肌转录本存在于心脏最早的功能阶段,并且这些TM同工型与整个心脏发育过程中存在的同工型相同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f49/359786/fc331069e12e/molcellb00018-0202-a.jpg

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