University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland; McMaster University, Faculty of Sciences, Department of Biology, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
Stem Cell Reports. 2023 Jul 11;18(7):1534-1546. doi: 10.1016/j.stemcr.2023.05.022.
Hematopoietic stem cells (HSCs) guarantee the continuous supply of all blood lineages during life. In response to stress, HSCs are capable of extensive proliferative expansion, whereas in steady state, HSCs largely remain in a quiescent state to prevent their exhaustion. DNA replication is a very complex process, where many factors need to exert their functions in a perfectly concerted manner. Mini-chromosome-maintenance protein 10 (Mcm10) is an important replication factor, required for proper assembly of the eukaryotic replication fork. In this report, we use zebrafish to study the role of mcm10 during embryonic development, and we show that mcm10 specifically regulates HSC emergence from the hemogenic endothelium. We demonstrate that mcm10-deficient embryos present an accumulation of DNA damages in nascent HSCs, inducing their apoptosis. This phenotype can be rescued by knocking down p53. Taken all together, our results show that mcm10 plays an important role in the emergence of definitive hematopoiesis.
造血干细胞（HSCs）保证了生命过程中所有血液谱系的持续供应。在应激反应下，HSCs 能够进行广泛的增殖扩张，而在稳态下，HSCs 主要处于静止状态，以防止其耗竭。DNA 复制是一个非常复杂的过程，其中许多因素需要以完美协调的方式发挥作用。微小染色体维持蛋白 10（Mcm10）是一种重要的复制因子，对于真核复制叉的正确组装是必需的。在本报告中，我们使用斑马鱼来研究 Mcm10 在胚胎发育过程中的作用，并表明 Mcm10 特异性地调节造血内皮细胞中 HSC 的出现。我们证明 Mcm10 缺陷的胚胎中新生 HSCs 积累了 DNA 损伤，导致其凋亡。这种表型可以通过敲低 p53 来挽救。总之，我们的结果表明 Mcm10 在定型造血的出现中发挥了重要作用。
