| Experiment Id | GSE81467 | Name | The transcription factor Gli3 promotes B cell development in the fetal liver through repression of Shh |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2023-11-27 |
| description | 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. RNA sequencing 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. 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. |
