title: A perisinusoidal niche for extramedullary haematopoiesis in the spleen.
abstract: Haematopoietic stresses mobilize haematopoietic stem cells (HSCs) from the bone marrow to the spleen and induce extramedullary haematopoiesis (EMH). However, the cellular nature of the EMH niche is unknown. Here we assessed the sources of the key niche factors, SCF (also known as KITL) and CXCL12, in the mouse spleen after EMH induction by myeloablation, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21(+) stromal cells, primarily around sinusoids in the red pulp, while Cxcl12 was expressed by a subset of Tcf21(+) stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21(+) stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells, or of Scf or Cxcl12 from Tcf21+ stromal cells, severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow haematopoiesis. Endothelial cells and Tcf21(+) stromal cells thus create a perisinusoidal EMH niche in the spleen, which is necessary for the physiological response to diverse haematopoietic stresses.
authors.affiliation: Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Inra
authors.affiliation: Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Bo O
authors.initials: BO
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Melih
authors.initials: M
authors.lastname: Acar
authors.affiliation: Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Malea M
authors.initials: MM
authors.lastname: Murphy
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: James
authors.initials: J
authors.lastname: Richardson
authors.affiliation: Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.|Department of Pediatrics and Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001772:Blood Cell Count; D054377:Chemokine CXCL12 / Q000172:deficiency / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D004920:Erythropoiesis; D005260:Female; D006411:Hematopoiesis, Extramedullary; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006470:Hemorrhage / Q000503:physiopathology; D008297:Male; D051379:Mice; D011247:Pregnancy; D013154:Spleen / Q000098:blood supply / Q000166:cytology* / Q000378:metabolism; D019089:Stem Cell Factor / Q000172:deficiency / Q000378:metabolism; D055153:Stem Cell Niche; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D054377:Chemokine CXCL12; D019089:Stem Cell Factor; C515256:Cxcl12 protein, mouse; C112923:Tcf21 protein, mouse