Minichromosome maintenance protein 10 (mcm10) regulates hematopoietic stem cell emergence in the zebrafish embryo

• Published in: Stem cell reports Vol. 18; no. 7; pp. 1534 - 1546
• Main Authors: Cacialli, Pietro, Dogan, Serkan, Linnerz, Tanja, Pasche, Corentin, Bertrand, Julien Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11-07-2023; Elsevier
• Subjects: Animals; apoptosis; Apoptosis - genetics; cell cycle; Cell Cycle Proteins; Female; Hemangioblasts; Hematopoietic Stem Cells; hemogenic endothelium; mcm10; Minichromosome Maintenance Proteins; p53; Zebrafish; Zebrafish Proteins; cell cycle; mcm10; apoptosis; zebrafish; hematopoietic stem cells; hemogenic endothelium; p53
• ISSN: 2213-6711; 2213-6711
• 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.
•Mcm10 regulates HSC specification from the hemogenic endothelium•Mcm10 ensures the stability of the genome in the proliferating hemogenic endothelium•Nascent HSCs undergo apoptosis in mcm10-deficient embryos
In this study, Bertrand and colleagues show that Mcm10 is necessary to the development of hematopoietic progenitors during the endothelial-to-hematopoiesis process, by guaranteeing the integrity of the genome. Indeed, the absence of mcm10 results in the accumulation of DNA breaks in the hemogenic endothelium, leading to premature p53-dependent apoptosis, suggesting that cell cycle progression is intimately linked to HSC emergence.