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| Status |
Public on Aug 03, 2011 |
| Title |
Non-overlapping functions for Notch1 and Notch3 during murine steady state thymic lymphopoiesis. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Notch1 signaling is absolutely essential for steady-state thymic lymphopoiesis, but the role of other Notch receptors, and their potential overlap with the function of Notch1, remains unclear. Here we show that like Notch1, Notch3 is differentially expressed by progenitor thymocytes, peaking at the DN3 progenitor stage. Using mice carrying a gene-trapped allele, we show that thymic cellularity is slightly reduced in the absence of Notch3, although progression through the defined sequence of TCR-αβ development is normal, as are NKT and TCRγδ cell production.
The absence of a profound effect from Notch3 deletion is not explained by residual function of the gene-trapped allele, since insertion mapping suggests that the targeted allele would not encode functional signaling domains. We also show that although Notch1 and Notch3 are co-expressed on some early intrathymic progenitors, the relatively mild phenotype seen after Notch3 deletion does not result from the compensatory function of Notch1, nor does Notch3 function explain the likewise mild phenotype seen after conditional (intrathymic) deletion of
Notch1. Our studies indicate that Notch1 and Notch3 carry out non-overlapping functions during thymocyte differentiation, and that while Notch1 is absolutely required early in the lymphopoietic process, neither receptor is essential at later stages.
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| Overall design |
Thymuses from 10 male C57BL6 mice at 5 weeks old were used for sorting thymocytes (DN1, DN2, DN3, preDP, DP). These samples were used for subsequent RNA purification, labeling and hybridization to Affymetrix arrays.
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| Contributor(s) |
Petrie HT, Shi J, Fallahi M |
| Citation(s) |
21768299, 15240698 |
| Submission date |
Jul 13, 2011 |
| Last update date |
Feb 18, 2018 |
| Contact name |
howard t petrie |
| E-mail(s) |
hpetrie@scripps.edu
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| Phone |
561 228 3205
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| Organization name |
the scripps research instititute
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| Department |
cancer biology
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| Street address |
130 scripps way
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| City |
jupiter |
| State/province |
FL |
| ZIP/Postal code |
33458 |
| Country |
USA |
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| Platforms (1) |
| GPL81 |
[MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array |
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| Samples (5)
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| GSM759775 |
lin- CD24+ CD25- CD44hi sorted thymocyte double negative DN1 |
| GSM759776 |
lin- CD24+ CD25+ CD44hi sorted thymocyte double negative DN2 |
| GSM759777 |
lin- CD24+ CD25+ CD44lo sorted thymocyte double negative DN3 |
| GSM759778 |
lin- CD24+ CD25- CD44lo sorted thymocyte pre-double positive |
| GSM759779 |
CD4+8+ sorted thymocyte double positive |
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| Relations |
| BioProject |
PRJNA144585 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30631_RAW.tar |
13.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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