title: PLZF mutation alters mouse hematopoietic stem cell function and cell cycle progression.
abstract: Hematopoietic stem cells (HSCs) give rise to all blood populations due to their long-term self-renewal and multipotent differentiation capacities. Because they have to persist throughout an organism's life span, HSCs tightly regulate the balance between proliferation and quiescence. Here, we investigated the role of the transcription factor promyelocytic leukemia zinc finger (plzf) in HSC fate using the Zbtb16(lu/lu)mouse model, which harbors a natural spontaneous mutation that inactivates plzf. Regenerative stress revealed that Zbtb16(lu/lu)HSCs had a lineage-skewing potential from lymphopoiesis toward myelopoiesis, an increase in the long-term-HSC pool, and a decreased repopulation potential. Furthermore, oldplzf-mutant HSCs present an amplified aging phenotype, suggesting that plzf controls age-related pathway. We found that Zbtb16(lu/lu)HSCs harbor a transcriptional signature associated with a loss of stemness and cell cycle deregulation. Lastly, cell cycle analyses revealed an important role for plzf in the regulation of the G1-S transition of HSCs. Our study reveals a new role for plzf in regulating HSC function that is linked to cell cycle regulation, and positions plzf as a key player in controlling HSC homeostasis.
authors.affiliation: INSERM U1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille University, Unité Mixte 105, Marseille, France; Centre national de la recherche scientifique, Unité mixte de recherche 7258, Centre de Recherche en Cancérologie de Marseille, Marseille, France; and.
authors.forename: Christelle
authors.initials: C
authors.lastname: Vincent-Fabert
authors.affiliation: INSERM U1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille University, Unité Mixte 105, Marseille, France; Centre national de la recherche scientifique, Unité mixte de recherche 7258, Centre de Recherche en Cancérologie de Marseille, Marseille, France; and.
authors.forename: Nadine
authors.initials: N
authors.lastname: Platet
authors.affiliation: INSERM U1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille University, Unité Mixte 105, Marseille, France; Centre national de la recherche scientifique, Unité mixte de recherche 7258, Centre de Recherche en Cancérologie de Marseille, Marseille, France; and.
authors.forename: Amelle
authors.initials: A
authors.lastname: Vandevelde
authors.affiliation: INSERM U1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille University, Unité Mixte 105, Marseille, France; Centre national de la recherche scientifique, Unité mixte de recherche 7258, Centre de Recherche en Cancérologie de Marseille, Marseille, France; and.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Poplineau
authors.affiliation: INSERM U1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille University, Unité Mixte 105, Marseille, France; Centre national de la recherche scientifique, Unité mixte de recherche 7258, Centre de Recherche en Cancérologie de Marseille, Marseille, France; and.
authors.forename: Myriam
authors.initials: M
authors.lastname: Koubi
authors.affiliation: INSERM U1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille University, Unité Mixte 105, Marseille, France; Centre national de la recherche scientifique, Unité mixte de recherche 7258, Centre de Recherche en Cancérologie de Marseille, Marseille, France; and.
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.affiliation: INSERM U1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille University, Unité Mixte 105, Marseille, France; Centre national de la recherche scientifique, Unité mixte de recherche 7258, Centre de Recherche en Cancérologie de Marseille, Marseille, France; and.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Tiberi
authors.affiliation: INSERM U1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France; Institut Paoli-Calmettes, Marseille, France; INSERM Centre d'Investigation Clinique en Biothérapie 1409, Marseille, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Imbert
authors.affiliation: INSERM U1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille University, Unité Mixte 105, Marseille, France; Centre national de la recherche scientifique, Unité mixte de recherche 7258, Centre de Recherche en Cancérologie de Marseille, Marseille, France; and.
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.affiliation: INSERM U1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Aix-Marseille University, Unité Mixte 105, Marseille, France; Centre national de la recherche scientifique, Unité mixte de recherche 7258, Centre de Recherche en Cancérologie de Marseille, Marseille, France; and.
authors.forename: Estelle
authors.initials: E
authors.lastname: Duprez
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D016922:Cellular Senescence; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006706:Homeostasis; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000502:physiology*; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D038042:Myelopoiesis; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D000075722:Promyelocytic Leukemia Zinc Finger Protein
chemical_list: D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse