Loss of the Homeodomain Transcription Factor Prep1 Perturbs Adult Hematopoiesis in the Bone Marrow.
Loss of the Homeodomain Transcription Factor Prep1 Perturbs Adult Hematopoiesis in the Bone Marrow.
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同源域转录因子Prep1的丧失骨髓中成年造血作用。
DOI：
10.1371/journal.pone.0136107
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Goitsuka R
中科院分区：
文献类型：
--
作者：
Yoshioka K;Oda A;Notsu C;Ohtsuka T;Kawai Y;Suzuki S;Nakamura T;Mabuchi Y;Matsuzaki Y;Goitsuka R
Prep1是一种TALE家族同源结构域转录因子，已被证明在胚胎造血中起关键作用，因为其不足导致与造血缺陷和血管生成相关的晚期胚胎致死。在本研究中，我们产生了造血和内皮细胞特异性Prep1缺陷小鼠，并证明了在造血细胞隔室中表达Prep1对于胚胎或成人造血不是必需的，尽管它的缺乏会导致成人骨髓中显著的造血异常。Prep1的缺失促进造血干/祖细胞（HSPC）的细胞循环，导致HSPC池扩增。Prep1缺陷还导致谱系定型祖细胞的积累，单核细胞/巨噬细胞分化增加和红细胞成熟停滞。T细胞和B细胞的成熟在Prep缺陷小鼠中也受到干扰。这些研究结果提供了新的见解，在成人造血的多效作用Prep1在以前的研究中未被认可的生殖系Prep1亚型小鼠。
Prep1, a TALE-family homeodomain transcription factor, has been demonstrated to play a critical role in embryonic hematopoiesis, as its insufficiency caused late embryonic lethality associated with defective hematopoiesis and angiogenesis. In the present study, we generated hematopoietic- and endothelial cell-specific Prep1-deficient mice and demonstrated that expression of Prep1 in the hematopoietic cell compartment is not essential for either embryonic or adult hematopoiesis, although its absence causes significant hematopoietic abnormalities in the adult bone marrow. Loss of Prep1 promotes cell cycling of hematopoietic stem/progenitor cells (HSPC), leading to the expansion of the HSPC pool. Prep1 deficiency also results in the accumulation of lineage-committed progenitors, increased monocyte/macrophage differentiation and arrested erythroid maturation. Maturation of T cells and B cells is also perturbed in Prep-deficient mice. These findings provide novel insight into the pleiotropic roles of Prep1 in adult hematopoiesis that were unrecognized in previous studies using germline Prep1 hypomorphic mice.