C/EBP-Induced Transdifferentiation Reveals Granulocyte-Macrophage Precursor-like Plasticity of B Cells.
C/EBP-Induced Transdifferentiation Reveals Granulocyte-Macrophage Precursor-like Plasticity of B Cells.
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DOI：
10.1016/j.stemcr.2016.12.015
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发表时间：
2017-02-14
影响因子：
5.9
通讯作者：
Leutz A
中科院分区：
文献类型：
--
作者：
Cirovic B;Schönheit J;Kowenz-Leutz E;Ivanovska J;Klement C;Pronina N;Bégay V;Leutz A
在v-Abl永生化的原代B细胞中，比较了C/eBP家族成员(C/eBPα，β，δ和ε)的淋系-髓系转分化潜能。任何C/EBp的异位表达均可诱导B细胞向巨噬细胞转化，内源性C/EBpα和β激活可促进B细胞向巨噬细胞转化。高表达C/eBPβ或C/eBPε，而不表达C/eBPα或C/eBPδ，也可诱导粒细胞的形成。粒细胞和巨噬细胞以相互排斥的方式出现。表达c/eBPβ的B细胞在选择性压力下产生粒-巨噬细胞样祖细胞，以消除淋巴样细胞。GMP样祖细胞保持自我更新和细胞因子非依赖性，并持续产生巨噬细胞和粒细胞。除了适合于研究粒单核细胞谱系的分叉外，谱系转换的GMP样祖细胞还可以反映白血病进展过程中观察到的淋巴-髓系转换的特征。反式激活C/eBP家族成员将B细胞转分化为髓系细胞C/eBPβ或C/eBPε将B细胞转分化为巨噬细胞，粒细胞转基因剂量决定粒细胞与巨噬细胞类型的结果C/eBP介导的B细胞转换诱导GMP样潜能在本文中，Leutz及其同事评估了四种C/eBP转录因子在B细胞中的转分化潜力。C/eBPβ和C/eBPε刺激巨噬细胞和粒细胞样细胞的形成。转分化涉及内源性C/EBP的激活。高转基因剂量促进粒细胞对巨噬细胞的转归。C/eBPβ还诱导出稳定的GMP样表型，可作为研究细胞命运决定的模型。
The lymphoid-myeloid transdifferentiation potentials of members of the C/EBP family (C/EBPα, β, δ, and ε) were compared in v-Abl-immortalized primary B cells. Conversion of B cells to macrophages was readily induced by the ectopic expression of any C/EBP, and enhanced by endogenous C/EBPα and β activation. High transgene expression of C/EBPβ or C/EBPε, but not of C/EBPα or C/EBPδ, also induced the formation of granulocytes. Granulocytes and macrophages emerged in a mutually exclusive manner. C/EBPβ-expressing B cells produced granulocyte-macrophage progenitor (GMP)-like progenitors when subjected to selective pressure to eliminate lymphoid cells. The GMP-like progenitors remained self-renewing and cytokine-independent, and continuously produced macrophages and granulocytes. In addition to their suitability to study myelomonocytic lineage bifurcation, lineage-switched GMP-like progenitors could reflect the features of the lympho-myeloid lineage switch observed in leukemic progression. Transactivating C/EBP family members transdifferentiate B cells to myeloid cells C/EBPβ or C/EBPε transdifferentiate B cells to macrophages and granulocytes Transgene dosage determines granulocyte versus macrophage cell-type outcome C/EBP-mediated B cell conversion elicits GMP-like potential In this article, Leutz and colleagues assessed the transdifferentiation potential of four C/EBP transcription factors in B cells. C/EBPβ and C/EBPε stimulated the formation of macrophage and granulocyte-like cells. Transdifferentiation involved endogenous C/EBP activation. High transgene dosage promoted granulocyte versus macrophage outcome. C/EBPβ also elicited a stable GMP-like phenotype that could serve as a model to study cell-fate decision.
新型淋巴祖细胞的BALB和HARVEY-MURINE肉瘤病毒转化。
影响因子：
15.3
作者：
Pierce, J H;Aaronson, S A
通讯作者：
Aaronson, S A