title: Lin28b reprograms adult bone marrow hematopoietic progenitors to mediate fetal-like lymphopoiesis.
abstract: The immune system develops in waves during ontogeny; it is initially populated by cells generated from fetal hematopoietic stem cells (HSCs) and later by cells derived from adult HSCs. Remarkably, the genetic programs that control these two distinct stem cell fates remain poorly understood. We report that Lin28b is specifically expressed in mouse and human fetal liver and thymus, but not in adult bone marrow or thymus. We demonstrate that ectopic expression of Lin28 reprograms hematopoietic stem/progenitor cells (HSPCs) from adult bone marrow, which endows them with the ability to mediate multilineage reconstitution that resembles fetal lymphopoiesis, including increased development of B-1a, marginal zone B, gamma/delta (γδ) T cells, and natural killer T (NKT) cells.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Yuan
authors.forename: Cuong K
authors.initials: CK
authors.lastname: Nguyen
authors.forename: Xiuhuai
authors.initials: X
authors.lastname: Liu
authors.forename: Chrysi
authors.initials: C
authors.lastname: Kanellopoulou
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Muljo
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D001854:Bone Marrow Cells / Q000378:metabolism; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D005333:Fetus; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000196:embryology / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D004268:DNA-Binding Proteins; C516326:LIN28B protein, human; C570876:Lin28b protein, mouse; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human; C542687:mirnlet7 microRNA, mouse