Cobaleda César, Busslinger Meinrad
Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
Curr Opin Immunol. 2008 Apr;20(2):139-48. doi: 10.1016/j.coi.2008.03.017. Epub 2008 May 9.
Experimental perturbation of signaling or transcription factor networks has been used to study the developmental potential of lymphoid progenitors, lineage-committed precursors and mature lymphocytes. Common lymphoid progenitors and uncommitted pro-T cells can be efficiently diverted into myeloid or erythroid lineages by ectopic cytokine signaling or retroviral expression of the myeloid C/EBPalpha or erythroid GATA1 transcription factor. Forced C/EBPalpha expression furthermore induces direct transdifferentiation of immature thymocytes or B cells into macrophages. Notably, conditional inactivation of the B cell commitment factor Pax5 is sufficient to convert mature B cells into functional T cells via dedifferentiation to uncommitted progenitors. Together these experiments have uncovered an unanticipated developmental plasticity of lymphocytes, which may account for lineage switches observed in human malignancies.
信号或转录因子网络的实验性扰动已被用于研究淋巴祖细胞、谱系定向前体细胞和成熟淋巴细胞的发育潜能。通过异位细胞因子信号传导或髓系C/EBPα或红系GATA1转录因子的逆转录病毒表达，常见淋巴祖细胞和未定向的前T细胞可以有效地转向髓系或红系谱系。此外，强制表达C/EBPα可诱导未成熟胸腺细胞或B细胞直接转分化为巨噬细胞。值得注意的是，B细胞定向因子Pax5的条件性失活足以通过去分化为未定向祖细胞将成熟B细胞转化为功能性T细胞。这些实验共同揭示了淋巴细胞意想不到的发育可塑性，这可能解释了在人类恶性肿瘤中观察到的谱系转换。
