Connexin 41.8 governs timely haematopoietic stem and progenitor cell specification.

IF 1.7 4区 生物学 Q3 BIOLOGY
Biology Open Pub Date : 2025-08-15 Epub Date: 2025-08-12 DOI:10.1242/bio.062118
Tim Petzold, Sarah Brivio, Tanja Linnerz, Masakatsu Watanabe, Holger Gerhardt, Julien Y Bertrand
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引用次数: 0

Abstract

Haematopoietic stem and progenitor cells (HSPCs) derive from a subset of endothelial cells (ECs), known as haemogenic ECs by the process of endothelial-to-haematopoietic transition (EHT). Although many factors involved in EHT have been elucidated, we still have a poor understanding of the temporal regulation of this process. Mitochondrial-derived reactive oxygen species (ROS) have been shown to stabilise the hypoxia-inducible factor 1/2α (Hif1/2α) proteins, allowing them to positively regulate EHT. Here, we show a developmental delay in EHT and HSPC induction in a connexin (cx)41.8 (orthologous to mammalian CX40) gap junction mutant, in zebrafish. In mammalian cells, CX40 has been shown to localise to the mitochondria. We demonstrate that Cx41.8 is important for the correct temporal generation of mitochondrial ROS, which stabilise the Hif pathway, allowing for the subsequent specification of the haemogenic endothelium. Taken together, our data indicate that Cx41.8 governs the correct temporal induction of HSPCs.

连接蛋白41.8控制及时的造血干细胞和祖细胞规范。
造血干细胞和祖细胞(HSPCs)来源于内皮细胞(ECs)的一个亚群,通过内皮细胞到造血细胞的转化(EHT)过程被称为造血内皮细胞。虽然许多与EHT相关的因素已经被阐明,但我们对这一过程的时间调控仍然知之甚少。线粒体来源的活性氧(ROS)已被证明可以稳定缺氧诱导因子1/2a (Hif1/2a)蛋白,使它们能够积极调节EHT。在这里,我们展示了斑马鱼缝隙连接突变体连接蛋白(cx)41.8(与哺乳动物CX40同源)中EHT和HSPC诱导的发育延迟。在哺乳动物细胞中,CX40已被证明定位于线粒体。我们证明了Cx41.8对于线粒体ROS的正确时间生成是重要的,它稳定了Hif途径,允许随后的造血内皮的规范。综上所述,我们的数据表明Cx41.8控制着HSPCs的正确时间诱导。
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来源期刊
Biology Open
Biology Open BIOLOGY-
CiteScore
3.90
自引率
0.00%
发文量
162
审稿时长
8 weeks
期刊介绍: Biology Open (BiO) is an online Open Access journal that publishes peer-reviewed original research across all aspects of the biological sciences. BiO aims to provide rapid publication for scientifically sound observations and valid conclusions, without a requirement for perceived impact.
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