FGFR2 is required for airway basal cell self-renewal and terminal differentiation

Airway stem cells slowly self-renew and produce differentiated progeny to maintain homeostasis throughout the lifespan of an individual. Mutations in the molecular regulators of these processes may drive cancer or degenerative disease, but are also potential therapeutic targets. Conditionally deleting one copy of FGF receptor 2 (FGFR2) in adult mouse airway basal cells results in self-renewal and differentiation phenotypes. We show that FGFR2 signalling correlates with maintenance of expression of a key transcription factor for basal cell self-renewal and differentiation: SOX2. This heterozygous phenotype illustrates that subtle changes in receptor tyrosine kinase signalling can have significant effects, perhaps providing an explanation for the numerous changes seen in cancer.This study was supported by the Medical Research Council (G0900424 to E.R.). Core funders were as follows: Wellcome Trust (092096) and Cancer Research UK (C6946/A14492) supporting the Gurdon Institute; Wellcome Trust and Medical Research Council supporting the Stem Cell Initiative

Immunosuppressive treatment during pregnancy as a potential factor changing magnesium, calcium and phosphorus levels in hard tissues of female rats and their offspring

Immunosuppressive therapy is necessary to prevent transplant rejection, also in the case of pregnant transplant recipients, which means that the medications may influence foetal development. An ideal immunosuppressive regimen should provide for excellent immunosuppression with minimal or no side effects. Yet, current immunosuppressive therapy regimens commonly used in clinical applications fail to meet this criterion. One of the complications caused by immunosuppressive drugs are mineralisation disorders in hard tissues. Therefore, in this study, we evaluated the impact of three regimens of immunosuppressive therapy used after renal transplantation, containing medications which are indicated (prednisone, cyclosporine A (CsA), tacrolimus (Tc)) and contraindicated (mycophenolate mofetil (MMF), everolimus) during pregnancy on the concentrations of essential minerals, calcium (Ca), phosphorus (P) and magnesium (Mg), affecting normal bone formation. The samples were analysed using inductively coupled plasma optical emission spectrometry (ICP-OES, ICAP 7400 Duo, Thermo Scientific) equipped with a concentric nebuliser and a cyclonic spray chamber. The immunosuppressive regimens under study had no effect on the levels of Mg and P, but they did contribute to increased bone Ca levels in the mothers in the group receiving Tc, MMF and prednisone and group receiving CsA, everolimus and prednisone. In the offspring of tested mother rats, immunosuppressive therapies may affect Mg levels in hard tissues. The immunosuppressive regimens administered at therapeutic doses are harmful to rat foetuses as evidenced by the small number or lack of offspring in the tested groups