Differential geminin requirement for proliferation of thymocytes and mature T cells.
Stem/progenitor cells coordinate proliferation and differentiation, giving rise to appropriate cell numbers of functionally specialized cells during organogenesis. In different experimental systems, Geminin was shown to maintain progenitor cells and participate in fate determination decisions and organogenesis. Although the exact mechanisms are unclear, Geminin has been postulated to influence proliferation versus differentiation decisions. To gain insight into the in vivo role of Geminin in progenitor cell division and differentiation, we have generated mice that specifically lack Geminin in cells of lymphoid lineage through Cre-mediated recombination. T cells lacking Geminin expression upregulate early activation markers efficiently upon TCR stimulation in vitro and are able to enter the S phase of cell cycle, but show a marked defect in completing the cycle, leading to a large proportion of T cells accumulating in S/G2/M phases. Accordingly, T cells deficient in Geminin show a reduced ability to repopulate lymphopenic hosts in vivo. Contrary to expectations, Geminin deficiency does not alter development and differentiation of T cells in vivo. Our data suggest that Geminin is required for the proliferation events taking place either in vitro upon TCR receptor activation or during homeostatic expansion, but appears to be redundant for the proliferation and differentiation of the majority of progenitor T cell populations.
Karamitros
Dimitris
D
Department of Pharmacology, Medical Research Council/National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom.
Kotantaki
Panorea
P
Lygerou
Zoi
Z
Veiga-Fernandes
Henrique
H
Pachnis
Vassilis
V
Kioussis
Dimitris
D
Taraviras
Stavros
S
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D016195:G2 Phase / Q000235:genetics / Q000502:physiology; D064248:Geminin; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D008221:Lymphoid Tissue / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016196:S Phase / Q000235:genetics / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D064248:Geminin; C577997:Gmnn protein, mouse; D009687:Nuclear Proteins; C498645:Ris2 protein, mouse