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

Pietro Cacialli1, Serkan Dogan2, Tanja Linnerz3

  • 1University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.

Stem Cell Reports
|July 12, 2023
PubMed

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.

Related Concept Videos