RESUMO
Hematopoietic stem cells (HSCs) located in adult bone marrow or fetal liver in mammals produce all cells from the blood system. At the top of the hierarchy are long-term HSCs endowed with lifelong self-renewal and differentiation properties. These features are controlled through key microenvironmental cues and regulatory pathways, such as Wnt signaling. We showed previously that PTK7, a tyrosine kinase receptor involved in planar cell polarity, plays a role in epithelial Wnt signaling; however, its function in hematopoiesis has remained unexplored. In this article, we show that PTK7 is expressed by hematopoietic stem and progenitor cells, with the highest level of protein expression found on HSCs. Taking advantage of a Ptk7-deficient mouse strain, we demonstrate that loss of Ptk7 leads to a diminished pool of HSCs but does not affect in vitro or in vivo hematopoietic cell differentiation. This is correlated with increased quiescence and reduced homing abilities of Ptk7-deficient hematopoietic stem and progenitor cells, unraveling novel and unexpected functions for planar cell polarity pathways in HSC fate.
Assuntos
Movimento Celular , Proliferação de Células , Hematopoese , Células-Tronco Hematopoéticas/citologia , Receptores Proteína Tirosina Quinases/genética , Animais , Adesão Celular , Linhagem Celular , Polaridade Celular , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de SinaisRESUMO
The CBL family of E3 ubiquitin ligases regulates cell signaling in a number of tissues by promoting degradation of tyrosine kinase receptors such as epidermal growth factor receptor. CBLC, the third member of the CBL family, is expressed in epithelial tissues, including the mammary gland. A transgenic mouse strain expressing a tetracyclin-inducible CBLC in the mammary gland was derived. It was found that CBLC transgene expression reduces the number and length of ducts during the development of the gland. In vivo results support the concept of CBLs as negative regulators of cell proliferation. Alternatively, the phenotype may be due to increased apoptosis. This mouse model may be used to further study regulatory components of the CBL pathway and may be crossed with mice susceptible to develop mammary tumors.