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泛素-绿色荧光蛋白小鼠中的干细胞缺陷促进淋巴样前体造血干细胞的植入。

Stem Cell Defect in Ubiquitin-Green Fluorescent Protein Mice Facilitates Engraftment of Lymphoid-Primed Hematopoietic Stem Cells.

机构信息

Institute of Pathological Physiology, First Faculty of Medicine, Charles University.

BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Institute of Pathological Physiology, Czech Republic.

出版信息

Stem Cells. 2018 Aug;36(8):1237-1248. doi: 10.1002/stem.2828. Epub 2018 Apr 15.

DOI:10.1002/stem.2828
PMID:29603838
Abstract

Transgenic mice expressing green fluorescent protein (GFP) are useful in transplantation experiments. When we used ubiquitin-GFP (UBC-GFP) transgenic mice to study the availability of niches for transplanted hematopoietic stem and progenitor cells, the results were strikingly different from the corresponding experiments that used congenic mice polymorphic in the CD45 antigen. Analysis of these unexpected results revealed that the hematopoiesis of UBC-GFP mice was outcompeted by the hematopoiesis of wild-type (WT) mice. Importantly, UBC-GFP mice engrafted the transplanted bone marrow of WT mice without conditioning. There was a significant bias toward lymphopoiesis in the WT branch of chimeric UBC-GFP/WT hematopoiesis. A fraction of immature Sca-1 cells in the spleen of UBC-GFP mice expressed GFP at a very high level. The chimeric hematopoiesis was stable in the long term and also after transplantation to secondary recipient mice. The article thus identifies a specific defect in the hematopoiesis of UBC-GFP transgenic mice that compromises the lymphoid-primed hematopoietic stem cells in the bone marrow and spleen. Stem Cells 2018;36:1237-1248.

摘要

表达绿色荧光蛋白(GFP)的转基因小鼠在移植实验中非常有用。当我们使用泛素-GFP(UBC-GFP)转基因小鼠来研究移植造血干细胞和祖细胞的龛位可用性时,结果与使用在 CD45 抗原上具有多态性的同基因小鼠进行的相应实验明显不同。对这些意外结果的分析表明,UBC-GFP 小鼠的造血作用被野生型(WT)小鼠的造血作用所竞争。重要的是,UBC-GFP 小鼠在没有条件的情况下植入了 WT 小鼠的骨髓移植。在嵌合 UBC-GFP/WT 造血中,WT 分支偏向于淋巴发生。UBC-GFP 小鼠脾脏中幼稚的 Sca-1 细胞的一部分以非常高的水平表达 GFP。嵌合造血在长期和移植到次级受者小鼠后也很稳定。因此,该文章确定了 UBC-GFP 转基因小鼠造血中的一个特定缺陷,该缺陷损害了骨髓和脾脏中淋巴样前体造血干细胞。干细胞 2018;36:1237-1248。

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