The expansion of thymopoiesis in neonatal mice is dependent on expression of high mobility group a 2 protein (Hmga2).
Cell number in the mouse thymus increases steadily during the first two weeks after birth. It then plateaus and begins to decline by seven weeks after birth. The factors governing these dramatic changes in cell production are not well understood. The data herein correlate levels of High mobility group A 2 protein (Hmga2) expression with these temporal changes in thymopoiesis. Hmga2 is expressed at high levels in murine fetal and neonatal early T cell progenitors (ETP), which are the most immature intrathymic precursors, and becomes almost undetectable in these progenitors after 5 weeks of age. Hmga2 expression is critical for the initial, exponential expansion of thymopoiesis, as Hmga2 deficient mice have a deficit of ETPs within days after birth, and total thymocyte number is repressed compared to wild type littermates. Finally, our data raise the possibility that similar events occur in humans, because Hmga2 expression is high in human fetal thymic progenitors and falls in these cells during early infancy.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America; Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.
Beata
B
Berent-Maoz
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.
Encarnacion
E
Montecino-Rodriguez
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.
Michael
M
Fice
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.
David
D
Casero
Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.
Christopher S
CS
Seet
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America; Department of Pediatrics, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.
Gay M
GM
Crooks
Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America.
William
W
Lowry
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.
Kenneth
K
Dorshkind
D000375:Aging / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D053686:Fetal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D025743:HMGA2 Protein / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D038081:Organogenesis / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000378:metabolism*
D015703:Antigens, CD; D025743:HMGA2 Protein