title: IL-7 mediates Ebf-1-dependent lineage restriction in early lymphoid progenitors.
abstract: Deficiencies in the IL-7 signaling pathway result in severe disruptions of lymphoid development in adult mice. To understand more about how IL-7 deficiency impacts early lymphoid development, we have investigated lineage restriction events within the common lymphoid progenitor (CLP) compartment in IL-7 knockout mice. This revealed that although IL-7 deficiency had a minor impact on the development of LY6D(-) multipotent CLPs, the formation of the lineage restricted LY6D(+) CLP population was dramatically reduced. This was reflected in a low-level transcription of B-lineage genes as well as in a loss of functional B-cell commitment. The few Ly6D(+) CLPs developed in the absence of IL-7 displayed increased lineage plasticity and low expression of Ebf-1. Absence of Ebf-1 could be linked to increased plasticity because even though Ly6D(+) cells develop in Ebf-1-deficient mice, these cells retain both natural killer and dendritic cell potential. This reveals that IL-7 is essential for normal development of Ly6D(+) CLPs and that Ebf-1 is crucial for lineage restriction in early lymphoid progenitors.
authors.affiliation: Department of Clinical and Experimental Medicine, Experimental Hematopoiesis Unit, Faculty for Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tsapogas
authors.forename: Sasan
authors.initials: S
authors.lastname: Zandi
authors.forename: Josefine
authors.initials: J
authors.lastname: Åhsberg
authors.forename: Jenny
authors.initials: J
authors.lastname: Zetterblad
authors.forename: Eva
authors.initials: E
authors.lastname: Welinder
authors.forename: Jan Ingvar
authors.initials: JI
authors.lastname: Jönsson
authors.forename: Robert
authors.initials: R
authors.lastname: Månsson
authors.forename: Hong
authors.initials: H
authors.lastname: Qian
authors.forename: Mikael
authors.initials: M
authors.lastname: Sigvardsson
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D058851:GPI-Linked Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D015851:Interleukin-7 / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D000950:Antigens, Ly; C489921:Ebf1 protein, mouse; D058851:GPI-Linked Proteins; D015851:Interleukin-7; C035271:Ly6d protein, mouse; D015534:Trans-Activators