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The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh

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. Green open access

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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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