title: Enhancing T lineage production in aged mice: a novel function of Foxn1 in the bone marrow niche.
abstract: Foxn1 is essential for thymic organogenesis and T lymphopoiesis. Whereas reduced Foxn1 expression results in a decline in T lymphopoiesis, overexpression of Foxn1 in the thymus of a transgenic mouse model (Foxn1Tg) attenuates the age-associated decline in T lymphopoiesis. T lymphopoiesis begins with early T cell progenitors (ETP), derived from multipotent progenitors (MPP) in the bone marrow (BM). A decline in MPP and ETP numbers with age is thought to contribute to reduced T lymphopoiesis. Previously, we showed that reduced ETP number with age is attenuated in Foxn1 transgenic (Tg); whether the effect is initiated in the BM with MPP is not known. In this study, we report that Foxn1 is expressed in wild-type BM and overexpressed in Foxn1Tg. With age, the number of MPP in Foxn1Tg was not reduced, and Foxn1Tg also have a larger pool of hematopoietic stem cells. Furthermore, the Foxn1Tg BM is more efficient in generating MPP. In contrast to MPP, common lymphoid progenitors and B lineage cell numbers were significantly lower in both young and aged Foxn1Tg compared with wild type. We identified a novel population of lineage(neg/low), CD45(pos) EpCAM(pos), SCA1(pos), CD117(neg), CD138(neg), MHCII(neg) cells as Foxn1-expressing BM cells that also express Delta-like 4. Thus, Foxn1 affects both T lymphopoiesis and hematopoiesis, and the Foxn1 BM niche may function in skewing MPP development toward T lineage progenitors.
authors.affiliation: Cell Biology, Neurobiology, and Anatomy Graduate Program, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153;
authors.forename: Erin C
authors.initials: EC
authors.lastname: Zook
authors.forename: Shubin
authors.initials: S
authors.lastname: Zhang
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Gerstein
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Witte
authors.forename: Phong T
authors.initials: PT
authors.lastname: Le
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016130:Immunophenotyping; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018655:Lymphocyte Count; D054503:Lymphoid Progenitor Cells / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055153:Stem Cell Niche / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019076:Transgenes / Q000235:genetics
chemical_list: D015703:Antigens, CD; D051858:Forkhead Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C090140:Whn protein; C064045:delta protein