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| Status |
Public on May 09, 2017 |
| Title |
The transcription factor Gli3 promotes B cell development in the fetal liver through repression of Shh |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Before birth B-cells develop in the fetal liver (FL). Here we show that Gli3 activity in the FL stroma is required for B-cell development. In the Gli3-deficient FL B-cell development was reduced at multiple stages, whereas the Sonic hedgehog (Shh)-deficient FL showed increased B-cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hedgehog (Hh)-reporter mouse showed that Shh signals directly to developing B-cells, and that Hh pathway activation was increased in developing B-cells from Gli3-deficient fetal liver. RNAsequencing confirmed that Hh-mediated transcription is increased in B-lineage cells from Gli3-deficient FL, and showed that these cells expressed reduced levels of B-lineage transcription factors and BCR/pre-BCR-signalling genes. We showed that expression of the master regulators of B-cell development, Ebf1 and Pax5, is reduced in developing B-cells from Gli3-deficient FL and increased in Shh-deficient FL, and that in vitro Shh-treatment or neutralisation can repress or induce their expression respectively.
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| Overall design |
Wildtype and Gli3 mutant (Gli3+/- and Gli3-/-) (n=2) embryonic day 17.5 fetal livers were sorted for CD19+B220+ cells. RNA extracted from these cells was sequenced to help understand the transcriptional changes governing B cell development in the Gli3 mutants.
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| Contributor(s) |
Crompton T, Solanki A |
| Citation(s) |
28533268 |
| Submission date |
May 16, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Tessa Crompton |
| Organization name |
UCL
|
| Department |
Immunobiology
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| Street address |
30 Guilford Street
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| City |
London |
| ZIP/Postal code |
WC1N 1EH |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA321725 |
| SRA |
SRP075207 |
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