Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity.
Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity.
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DOI：
10.1084/jem.20110447
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发表时间：
2011-11-21
期刊：
影响因子：
--
通讯作者：
Kurokawa M
中科院分区：
文献类型：
--
作者：
Kataoka K;Sato T;Yoshimi A;Goyama S;Tsuruta T;Kobayashi H;Shimabe M;Arai S;Nakagawa M;Imai Y;Kumano K;Kumagai K;Kubota N;Kadowaki T;Kurokawa M
一只新的小鼠将IRES-GFP盒插入到Evi1基因座上，发现HSC的长期多系再繁殖活动与Evi1转录因子的表达特异性分离。亲水性病毒整合位点1是SET/PR结构域蛋白家族的一种转录因子，在小鼠的造血干细胞(HSCs)维持中起重要作用，并在多种髓系恶性肿瘤中过表达。在这里，我们产生了报告小鼠，其中内部核糖体进入位点(IRES)-GFP盒被敲入到Evi1基因座。利用这些小鼠，我们发现Evi1主要表达在成人骨髓的长期造血干细胞(LT-HSCs)，以及胚胎的主动脉-性腺-中肾、胎盘和胎肝的造血干/祖细胞部分。在胎儿和成人的造血系统中，Evi1的表达标志着细胞具有长期的多系再繁殖活性。当与传统的HSC表面标记相结合时，根据Evi1的表达进行分选可以显著提高具有HSC活性的细胞的纯化。Evi1杂合性导致LT-HSCs的自我更新能力明显受损，而过度表达Evi1则抑制分化并增强自我更新活性。重新引入Evi1，而不是Mds1-Evi1，挽救了由Evi1杂合性引起的HSC缺陷。因此，除了记录Evi1表达和HSC自我更新活性之间的特定关系外，这些发现还突出了Evi1-IRES-GFP报告小鼠在鉴定和分选功能性HSC方面的作用。
A new mouse in which an IRES-GFP cassette is knocked-in to the Evi1 locus reveals that HSC long-term multilineage repopulating activity specifically segregates with expression of the Evi1 transcription factor. Ecotropic viral integration site 1 (Evi1), a transcription factor of the SET/PR domain protein family, is essential for the maintenance of hematopoietic stem cells (HSCs) in mice and is overexpressed in several myeloid malignancies. Here, we generate reporter mice in which an internal ribosome entry site (IRES)-GFP cassette is knocked-in to the Evi1 locus. Using these mice, we find that Evi1 is predominantly expressed in long-term HSCs (LT-HSCs) in adult bone marrow, and in the hematopoietic stem/progenitor fraction in the aorta-gonad-mesonephros, placenta, and fetal liver of embryos. In both fetal and adult hematopoietic systems, Evi1 expression marks cells with long-term multilineage repopulating activity. When combined with conventional HSC surface markers, sorting according to Evi1 expression markedly enhances purification of cells with HSC activity. Evi1 heterozygosity leads to marked impairment of the self-renewal capacity of LT-HSCs, whereas overexpression of Evi1 suppresses differentiation and boosts self-renewal activity. Reintroduction of Evi1, but not Mds1-Evi1, rescues the HSC defects caused by Evi1 heterozygosity. Thus, in addition to documenting a specific relationship between Evi1 expression and HSC self-renewal activity, these findings highlight the utility of Evi1-IRES-GFP reporter mice for the identification and sorting of functional HSCs.
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小鼠骨髓中多能间充质干细胞的前瞻性鉴定、分离和系统移植。
DOI：
10.1084/jem.20091046
发表时间：
2009-10-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Morikawa S;Mabuchi Y;Kubota Y;Nagai Y;Niibe K;Hiratsu E;Suzuki S;Miyauchi-Hara C;Nagoshi N;Sunabori T;Shimmura S;Miyawaki A;Nakagawa T;Suda T;Okano H;Matsuzaki Y
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通讯作者：
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20.3
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通讯作者：
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Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
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Ramalho-Santos, M;Yoon, S;Melton, DA
通讯作者：
Melton, DA