LRRC10在心脏再生过程中调控哺乳动物心肌细胞周期。

IF 6.4 1区 医学 Q1 CELL & TISSUE ENGINEERING
Rebecca J Salamon, Megan C McKeon, Jiyoung Bae, Xiaoya Zhang, Wyatt G Paltzer, Kayla N Wanless, Alyssa R Schuett, Dakota J Nuttall, Stephen A Nemr, Rupa Sridharan, Youngsook Lee, Timothy J Kamp, Ahmed I Mahmoud
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引用次数: 1

摘要

Leucine-rich repeat containing 10 (LRRC10)是一种心肌细胞特异性蛋白,但其在心脏生物学中的作用尚不清楚。最近发现Lrrc10是斑马鱼内源性心脏再生所必需的;然而,LRRC10是否在哺乳动物心脏再生中发挥作用尚不清楚。在这项研究中,我们证明Lrrc10-/-敲除小鼠表现出新生小鼠再生反应的丧失,其标志是心肌细胞胞质分裂减少和心肌细胞双核增加。有趣的是,LRRC10缺失破坏了新生小鼠心脏再生的再生转录景观。值得注意的是,心脏过表达LRRC10可以恢复心肌细胞的细胞分裂,增加心肌细胞的单核细胞,并提高LRRC10 -/-小鼠的心脏再生能力。我们的结果与LRRC10在哺乳动物心脏再生过程中是心肌细胞胞质分裂和转录调控所必需的模型一致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

LRRC10 regulates mammalian cardiomyocyte cell cycle during heart regeneration.

LRRC10 regulates mammalian cardiomyocyte cell cycle during heart regeneration.

LRRC10 regulates mammalian cardiomyocyte cell cycle during heart regeneration.

Leucine-rich repeat containing 10 (LRRC10) is a cardiomyocyte-specific protein, but its role in cardiac biology is little understood. Recently Lrrc10 was identified as required for endogenous cardiac regeneration in zebrafish; however, whether LRRC10 plays a role in mammalian heart regeneration remains unclear. In this study, we demonstrate that Lrrc10-/- knockout mice exhibit a loss of the neonatal mouse regenerative response, marked by reduced cardiomyocyte cytokinesis and increased cardiomyocyte binucleation. Interestingly, LRRC10 deletion disrupts the regenerative transcriptional landscape of the regenerating neonatal mouse heart. Remarkably, cardiac overexpression of LRRC10 restores cardiomyocyte cytokinesis, increases cardiomyocyte mononucleation, and the cardiac regenerative capacity of Lrrc10-/- mice. Our results are consistent with a model in which LRRC10 is required for cardiomyocyte cytokinesis as well as regulation of the transcriptional landscape during mammalian heart regeneration.

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来源期刊
npj Regenerative Medicine
npj Regenerative Medicine Engineering-Biomedical Engineering
CiteScore
10.00
自引率
1.40%
发文量
71
审稿时长
12 weeks
期刊介绍: Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.
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