Solanki, A;
Lau, C-I;
Saldana, JI;
Ross, S;
Crompton, T;
(2017)
The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh.
Journal of Experimental Medicine
, 214
(7)
pp. 2041-2057.
10.1084/jem.20160852.
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Abstract
Before birth, B cells develop in the fetal liver (FL). In this study, 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 (Hh [Shh])–deficient FL showed increased B cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic 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 FLs. 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 B cell receptor (BCR)/pre-BCR–signaling genes. Expression of the master regulators of B cell development Ebf1 and Pax5 was reduced in developing B cells from Gli3-deficient FL but increased in Shh-deficient FL, and in vitro Shh treatment or neutralization reduced or increased their expression, respectively.
| Type: | Article |
|---|---|
| Title: | The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1084/jem.20160852 |
| Publisher version: | http://doi.org/10.1084/jem.20160852 |
| Language: | English |
| Additional information: | © 2017 Solanki et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Immunology, Medicine, Research & Experimental, Research & Experimental Medicine, HEDGEHOG-SIGNALING PATHWAY, SONIC HEDGEHOG, GENE-EXPRESSION, DIFFERENTIATION, ACTIVATION, THYMOCYTE, MOUSE, LYMPHOPOIESIS, LINEAGE, THYMUS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1558500 |
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