CD45lowc-Kithigh cells have hematopoietic properties in the mouse aorta-gonad-mesonephros region

CD45lowc-Kithigh cells have hematopoietic properties in the mouse aorta-gonad-mesonephros region
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DOI:
10.1016/j.yexcr.2012.01.017
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发表时间:
2012-04-01
影响因子:
3.7
通讯作者:
Taga, Tetsuya
Taga, Tetsuya
中科院分区:
医学3区
文献类型:
--
作者:
Nobuhisa, Ikuo;Yamasaki, Shoutarou;Taga, Tetsuya

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在小鼠胚胎中,长期重建的造血干细胞首先来自主动脉-性腺-中肾(AGM)区域的主动脉。我们先前已经报道,在分散的AGM区域的培养中,CD45(Low)c-Kit(+)细胞具有重建多系造血细胞的能力,但需要进行研究来证明这不是培养的产物,并根据新鲜分离的AGM细胞(E9.5-E12.5)和AGM(E13.5-E15.5)中CD45(-)和c-Kit(-)的表达谱来阐明这个群体何时以及如何存在。CD45(-)c-Kit(高)、CD45(低)c-Kit(高)、CD45(高)c-Kit(高)、CD45(高)c-Kit(非常低))。在这6个群体中,CD45(低)c-Kit(高)细胞最有能力形成造血细胞集落,但其能力在E11.5以后下降,在E13.5及以后检测不到。CD45(低)c-Kit(高)细胞在体外表现出多潜能。我们证明了在CD45(低)-Kit(高)细胞中,Hoechst染料流出侧群体中的造血活性进一步丰富。在这里,我们利用胚胎干细胞来源的分化系统确定CD45(低)c-Kit(高)细胞起源于侧板中胚层。结论:CD45(低)c-Kit(高)细胞是小鼠急性粒细胞白血病的主要造血细胞。(C)2012 Elsevier Inc.保留所有权利。
Long-term reconstituting hematopoietic stem cells first arise from the aorta of the aorta-gonad-mesonephros (AGM) region in a mouse embryo. We have previously reported that in cultures of the dispersed AGM region, CD45(low)c-Kit(+) cells possess the ability to reconstitute multilineage hematopoietic cells, but investigations are needed to show that this is not a cultured artifact and to clarify when and how this population is present Based on the expression profile of CD45 and c-Kit in freshly dissociated AGM cells from embryonic day 9.5 (E9.5) to E12.5 and aorta cells in the AGM from E13.5 to E15.5, we defined six cell populations (CD45(-)c-Kit(-), CD45(-)c-Kit(low), CD45(-)c-Kit(high), CD45(low)c-Kit(high), CD45(high)c-Kit(high), CD45(high)c-Kit(very low)). Among these six populations, CD45(low)c-Kit(high) cells were most able to form hematopoietic cell colonies, but their ability decreased after E11.5 and was undetectable at E13.5 and later. The CD45(low)c-Kit(high) cells showed multipotency in vitro. We demonstrated further enrichment of hematopoietic activity in the Hoechst dye-effluxing side population among the CD45(low)-Kit(high) cells. Here, we determined that CD45(low)c-Kit(high) cells arise from the lateral plate mesoderm using embryonic stem cell-derived differentiation system. In conclusion, CD45(low)c-Kit(high) cells are the major hematopoietic cells of mouse AGM. (C) 2012 Elsevier Inc. All rights reserved.