title: On the adaptation of endosteal stem cell niche function in response to stress.
abstract: Although the influence of microenvironmental "niche" on the function of a variety of stem cells is undisputed, the details of hematopoietic stem cell/niche interactions at the cellular and molecular level have sparked a continuous debate. We studied the microanatomic partitioning of transplanted normal and alpha4 integrin-deficient Lin-kit+ cells in trabecular and compact bone before and after irradiation and present robust quantitative data on both. We found that (1) the microanatomic distribution of normal highly enriched progenitor cells is random in nonirradiated recipients based on area distribution analyses, (2) in contrast, in irradiated hosts normal cells distribute preferentially near the endosteum, (3) the overall cell seeding efficiency was higher in trabecular versus compact bone both before and after irradiation, and (4) alpha4 integrin-deficient cells not only lodge with reduced overall efficiency confirming previous data, but fail to preferentially partition themselves into endosteal regions in irradiated hosts, as normal cells do. A similar phenotype was observed with cells rendered G(i)-protein signaling incompetent by pertussis toxin treatment, supporting an active stromal-derived factor 1 (SDF-1) gradient near endosteum after irradiation.
authors.affiliation: University of Washington, Department of Medicine/Hematology, Seattle, WA 98195, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Halvard
authors.initials: H
authors.lastname: Bonig
authors.forename: Tatiana
authors.initials: T
authors.lastname: Ulyanova
authors.forename: KaiHsin
authors.initials: K
authors.lastname: Chang
authors.forename: Thalia
authors.initials: T
authors.lastname: Papayannopoulou
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism; D039441:Integrin alpha4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D037342:Pertussis Toxin / Q000235:genetics / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D013312:Stress, Physiological; D014916:Whole-Body Irradiation
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D039441:Integrin alpha4; D037342:Pertussis Toxin; D019009:Proto-Oncogene Proteins c-kit; D019206:GTP-Binding Protein alpha Subunits, Gi-Go