Tmem30a Plays Critical Roles in Ensuring the Survival of Hematopoietic Cells and Leukemia Cells in Mice
Tmem30a Plays Critical Roles in Ensuring the Survival of Hematopoietic Cells and Leukemia Cells in Mice
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Tmem30a 在确保小鼠造血细胞和白血病细胞的存活中发挥关键作用
DOI：
10.1016/j.ajpath.2018.02.015
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发表时间：
2018-06-01
影响因子：
6
通讯作者：
Hu, Yiguo
中科院分区：
文献类型：
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作者：
Li, Ning;Yang, Yeming;Hu, Yiguo
真核细胞质膜的基本结构是磷脂双分子层，其包含四种主要磷脂。这些磷脂不对称地分布在外小叶和内小叶之间。P4-ATP酶翻转酶复合物在确保这种不对称性中发挥重要作用。我们发现，条件性缺失Tmem 30 a，P4-ATP酶翻转酶复合物的β亚基，引起小鼠全血细胞减少。Tmem 30 a缺乏导致外周血、脾和骨髓中的谱系定型血细胞的耗竭。Tmem 30 a的消融还引起造血干细胞（HSC）的耗竭。HSC RNA测序结果显示，多个生物过程和信号通路参与了该事件，包括哺乳动物雷帕霉素信号转导靶点、HSC干细胞基因和干扰素应答基因。我们的研究结果还表明，靶向Tmem 30 a信号传导在BCR/ABL 1诱导的慢性髓性白血病中具有治疗效用。
The fundamental structure of eukaryotic cell plasma membrane is the phospholipid bilayer, which contains four major phospholipids. These phospholipids are asymmetrically distributed between the outer and inner leaflets. P4-ATPase flippase complexes play essential roles in ensuring this asymmetry. We found that conditional deletion of Tmem30a, the beta subunit of P4-ATPase flippase complex, caused pancytopenia in mice. Tmem30a deficiency resulted in depletion of lineage-committed blood cells in the peripheral blood, spleen, and bone marrow. Ablation of Tmem30a also caused the depletion of hematopoietic stem cells (HSCs). HSC RNA sequencing results revealed that multiple biological processes and signal pathways were involved in the event, including mammalian target of rapamycin signaling, genes for HSC sternness, and genes responding to interferons. Our results also revealed that targeting Tmem30a signaling had therapeutic utility in BCR/ABL1-induced chronic myeloid leukemia.