Enhancing T lineage production in aged mice: a novel function of Foxn1 in the bone marrow niche Journal Article

Authors: Zook, E. C.; Zhang, S; Gerstein, R. M.; Witte, P. L.; Le, P. T.
Article 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.
Journal Title: Journal of Immunology
Volume: 191
Issue: 11
ISSN: 1550-6606
Publisher: Unknown  
Journal Place: United States
Date Published: 2013
Start Page: 5583
End Page: 5593
Language: eng
Notes: LR: 20141202; GR: R01 AG013874/AG/NIA NIH HHS/United States; GR: R01 AG023809/AG/NIA NIH HHS/United States; GR: R01 AG32809/AG/NIA NIH HHS/United States; GR: T32 AG031780/AG/NIA NIH HHS/United States; GR: T32 AI007508/AI/NIAID NIH HHS/United States; JID: 2985117R; 0 (Antigens, CD); 0 (Forkhead Transcription Factors); 0 (Intracellular Signaling Peptides and Proteins); 0 (Membrane Proteins); 0 (Whn protein); 0 (delta protein); NIHMS528611; OID: NLM: NIHMS528611; OID: NLM: PMC4081451; 2013/11/01 [aheadofprint]; ppublish