title: Nkx2-5(+)islet1(+) mesenchymal precursors generate distinct spleen stromal cell subsets and participate in restoring stromal network integrity.
abstract: Secondary lymphoid organ stromal cells comprise different subsets whose origins remain unknown. Herein, we exploit a genetic lineage-tracing approach to show that splenic fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs), marginal reticular cells (MRCs), and mural cells, but not endothelial cells, originate from embryonic mesenchymal progenitors of the Nkx2-5(+)Islet1(+) lineage. This lineage include embryonic mesenchymal cells with lymphoid tissue organizer (LTo) activity capable also of supporting ectopic lymphoid-like structures and a subset of resident spleen stromal cells that proliferate and regenerate the splenic stromal microenvironment following resolution of a viral infection. These findings identify progenitor cells that generate stromal diversity in spleen development and repair and suggest the existence of multipotent stromal progenitors in the adult spleen with regenerative capacity.
authors.affiliation: Division of Molecular Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Castagnaro
authors.forename: Elisa
authors.initials: E
authors.lastname: Lenti
authors.forename: Sara
authors.initials: S
authors.lastname: Maruzzelli
authors.forename: Laura
authors.initials: L
authors.lastname: Spinardi
authors.forename: Edoardo
authors.initials: E
authors.lastname: Migliori
authors.forename: Diego
authors.initials: D
authors.lastname: Farinello
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sitia
authors.forename: Zachary
authors.initials: Z
authors.lastname: Harrelson
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
authors.forename: Luca G
authors.initials: LG
authors.lastname: Guidotti
authors.forename: Richard P
authors.initials: RP
authors.lastname: Harvey
authors.forename: Andrea
authors.initials: A
authors.lastname: Brendolan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D020566:Dendritic Cells, Follicular / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000503:physiopathology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012038:Regeneration; D013154:Spleen / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1