The generation of a Bcl11a lineage tracing mouse model

Abstract

The transcription factor B-cell lymphoma/leukaemia 11A (BCL11A) has essential functions in physiological processes as well as haematological and solid malignancies, however, its contribution to tissue development and tumour progression is poorly understood. Here we show the generation of a Bcl11a lineage tracing mouse model to allow for in vivo tracking of Bcl11a-expressing cells and their progeny. We validate the model in the mammary gland by using flow cytometry and whole-tissue 3D imaging to locate labelled cells after induction of tracing in early development. We show that Bcl11a is predominantly expressed in long-lived luminal progenitors which populate mammary alveoli upon pregnancy, confirming bona fide labelling of Bcl11a cells. The Bcl11a lineage tracing mouse model therefore provides a powerful resource to study Bcl11a cells in development, homeostasis, and cancer.

The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons

“…This method is based on a reporter construct in which expression of a fluorescent protein is driven by a tetracycline response element (TRE) in a Cre-dependent manner (Madisen et al, 2015;Poulin et al, 2018). We first combined the intersectional reporter mouse line Ai82D (Madisen et al, 2015) with a Dat tTA (tetracycline trans-activator driven by the Dat promoter) and a Bcl11a CreER mouse line (Chen et al, 2015;Poulin et al, 2018;Pensa et al, 2021;Figure 3A). Because BCL11A expression is already restricted to mDA subsets during embryogenesis (Figures S2F-S2I), CreER was activated by administering tamoxifen to pregnant females at E15.5 (Figure 3B).…”

“…Bcl11a flox mice (Wiegreffe et al, 2015) were kindly provided by Pengtao Liu, School of Biomedical Sciences, The University of Hong Kong, China; and Neal Copeland, Institute for Academic Medicine, Houston Methodist and obtained from Stefan Britsch, University of Ulm. Bcl11a CreER mice (Pensa et al, 2021) were kindly provided by Walid Khaled, Department of Pharmacology, University of Cambridge. Bcl11a cko mice were generated by crossing Dat IRES-Cre mice (Ba ¨ckman et al, 2006) with Bcl11a flox mice (Genotype: Dat RES-Cre/+ , Bcl11a flox/flox ).…”