title: Deubiquitinase MYSM1 Is Essential for Normal Fetal Liver Hematopoiesis and for the Maintenance of Hematopoietic Stem Cells in Adult Bone Marrow.
abstract: MYSM1 is a chromatin-interacting deubiquitinase recently shown to be essential for hematopoietic stem cell (HSC) function and normal progression of hematopoiesis in both mice and humans. However, it remains unknown whether the loss of function in Mysm1-deficient HSCs is due to the essential role of MYSM1 in establishing the HSC pool during development or due to a continuous requirement for MYSM1 in adult HSCs. In this study we, for the first time, address these questions first, by performing a detailed analysis of hematopoiesis in the fetal livers of Mysm1-knockout mice, and second, by assessing the effects of an inducible Mysm1 ablation on adult HSC functions. Our data indicate that MYSM1 is essential for normal HSC function and progression of hematopoiesis in the fetal liver. Furthermore, the inducible knockout model demonstrates a continuous requirement for MYSM1 to maintain HSC functions and antagonize p53 activation in adult bone marrow. These studies advance our understanding of the role of MYSM1 in HSC biology, and provide new insights into the human hematopoietic failure syndrome resulting from MYSM1 deficiency.
authors.affiliation: 1 Department of Physiology, McGill University , Montreal, Quebec, Canada .|2 Complex Traits Group, McGill University , Montreal, Quebec, Canada .
authors.forename: Michael
authors.initials: M
authors.lastname: Förster
authors.affiliation: 1 Department of Physiology, McGill University , Montreal, Quebec, Canada .|2 Complex Traits Group, McGill University , Montreal, Quebec, Canada .
authors.forename: Jad I
authors.initials: JI
authors.lastname: Belle
authors.affiliation: 1 Department of Physiology, McGill University , Montreal, Quebec, Canada .|2 Complex Traits Group, McGill University , Montreal, Quebec, Canada .
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Petrov
authors.affiliation: 3 Wellcome Trust Sanger Institute , Hinxton, Cambridge, United Kingdom .
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Ryder
authors.affiliation: 3 Wellcome Trust Sanger Institute , Hinxton, Cambridge, United Kingdom .
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.affiliation: 1 Department of Physiology, McGill University , Montreal, Quebec, Canada .|2 Complex Traits Group, McGill University , Montreal, Quebec, Canada .
authors.forename: Anastasia
authors.initials: A
authors.lastname: Nijnik
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015534:Trans-Activators; D064570:Ubiquitin-Specific Proteases
chemical_list: D015534:Trans-Activators; D010450:Endopeptidases; C570173:MYSM1 protein, mouse; D064570:Ubiquitin-Specific Proteases