title: Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs.
abstract: Hematopoietic stem cells (HSCs) are maintained through the regulation of symmetric and asymmetric cell division. We report that conditional ablation of the RNA-binding protein Msi2 results in a failure of HSC maintenance and engraftment caused by a loss of quiescence and increased commitment divisions. Contrary to previous studies, we found that these phenotypes were independent of Numb. Global transcriptome profiling and RNA target analysis uncovered Msi2 interactions at multiple nodes within pathways that govern RNA translation, stem cell function, and TGF-β signaling. Msi2-null HSCs are insensitive to TGF-β-mediated expansion and have decreased signaling output, resulting in a loss of myeloid-restricted HSCs and myeloid reconstitution. Thus, Msi2 is an important regulator of the HSC translatome and balances HSC homeostasis and lineage bias.
authors.affiliation: Molecular Pharmacology and Chemistry Program, 2 Center for Cell Engineering, and 3 Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065.
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Park
authors.forename: Raquel P
authors.initials: RP
authors.lastname: Deering
authors.forename: Yuheng
authors.initials: Y
authors.lastname: Lu
authors.forename: Patrick
authors.initials: P
authors.lastname: Tivnan
authors.forename: Steve
authors.initials: S
authors.lastname: Lianoglou
authors.forename: Fatima
authors.initials: F
authors.lastname: Al-Shahrour
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Ebert
authors.forename: Nir
authors.initials: N
authors.lastname: Hacohen
authors.forename: Christina
authors.initials: C
authors.lastname: Leslie
authors.forename: George Q
authors.initials: GQ
authors.lastname: Daley
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lengner
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kharas
mesh_terms: D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D003114:Colony-Forming Units Assay; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017931:DNA Primers; C499059:Msi2h protein, mouse; D016601:RNA-Binding Proteins