Document Detail

Computational modelling of T-cell formation kinetics: output regulated by initial proliferation-linked deferral of developmental competence.
MedLine Citation:
PMID:  23152106     Owner:  NLM     Status:  MEDLINE    
Bone-marrow-derived progenitors must continually enter the thymus of an adult mouse to sustain T-cell homeostasis, yet only a few input cells per day are sufficient to support a yield of 5 × 10(7) immature T-cells per day and an eventual output of 1-2 × 10(6) mature cells per day. While substantial progress has been made to delineate the developmental pathway of T-cell lineage commitment, still little is known about the relationship between differentiation competence and the remarkable expansion of the earliest (DN1 stage) T-cell progenitors. To address this question, we developed computational models where the probability to progress to the next stage (DN2) is related to division number. To satisfy differentiation kinetics and overall cell yield data, our models require that adult DN1 cells divide multiple times before becoming competent to progress into DN2 stage. Our findings were subsequently tested by in vitro experiments, where putative early and later-stage DN1 progenitors from the thymus were purified and their progression into DN2 was measured. These experiments showed that the two DN1 sub-populations divided with similar rates, but progressed to the DN2 stage with different rates, thus providing experimental evidence that DN1 cells increase their commitment probability in a cell-intrinsic manner as they undergo cell division. Proliferation-linked shifts in eligibility of DN1 cells to undergo specification thus control kinetics of T-cell generation.
Erica Manesso; Vijay Chickarmane; Hao Yuan Kueh; Ellen V Rothenberg; Carsten Peterson
Related Documents :
24846106 - Cryopreservation of porcine aortic heart valve leaflet-derived myofibroblasts.
23399116 - Chitosan biopolymer for fuel cell applications.
24337846 - Effects of pi3k inhibitor nvp-bkm120 on acquired resistance to gefitinib of human lung ...
23231916 - Enhancement of the diesel oil degradation ability of a marine bacterial strain by immob...
6685736 - The effect of platelet-derived growth factor on morphology and motility of human glial ...
2752976 - Development and characterization of a variant gc cell line with l-triiodothyronine-inde...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the Royal Society, Interface / the Royal Society     Volume:  10     ISSN:  1742-5662     ISO Abbreviation:  J R Soc Interface     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-11-15     Completed Date:  2013-04-19     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  101217269     Medline TA:  J R Soc Interface     Country:  England    
Other Details:
Languages:  eng     Pagination:  20120774     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cell Differentiation / immunology*
Cell Division / immunology*
Computer Simulation*
Models, Immunological*
T-Lymphocytes / cytology,  immunology*
Thymus Gland / cytology,  immunology*
Grant Support

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  The workings of the maximum entropy principle in collective human behaviour.
Next Document:  Antiproliferative effects of kisspeptin?10 depend on artificial GPR54 (KISS1R) expression levels.