Apoptosis Protection by the Epo Target Bcl-XL Allows Factor-Independent Differentiation of Primary Erythroblasts

摘要: Abstract Background: Erythropoietin (Epo) is required for correct execution of the erythroid differentiation program. Erythropoiesis requires Bcl-X L , a major late target Epo-receptor signaling. Mice lacking die around embryonic age E12.5, forming normal progenitors but functional red cells. Recently, serum-free culture conditions expansion murine cell were developed, yielding cells capable in vivo-like terminal into enucleated erythrocytes, response to Epo/insulin. Here we address whether Epo function during maturation involves cytokine-independent "default program," requiring only apoptosis inhibition through Epo-dependent upregulation . Results: Exogenous expression or Bcl-2 primary erythroblasts clonal erythroblast lines derived from p53 −/− mice allowed these undergo maturation, complete absence cytokines. A potential autocrine loop was ruled out by respective neutralizing antibodies. Importantly, sustained proliferation -expressing immature still factors (Epo, stem factor [SCF], and glucocorticoid receptor ligand dexamethasone [Dex]). Epo-independent - Bcl-2-expressing, thus triggered removal renewal SCF Dex. This initiated maturation-specific cascade transcription factors, followed divisions (characterized short G1 phase decrease size), hemoglobin accumulation, enucleation. Conclusions: During regulates numbers via inhibition, caused antiapoptotic protein allows "default" apoptosis-protected, committed erythroblasts, independent any exogenous signals.