Flk-2是造血干细胞分化的标志物：一种分离长期干细胞的简单方法。,Proceedings of the National Academy of Sciences of the United States of America

当前位置： X-MOL 学术 › Proc. Natl. Acad. Sci. U.S.A. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Flk-2是造血干细胞分化的标志物：一种分离长期干细胞的简单方法。
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2001 Dec 4 , DOI: 10.1073/pnas.261562798
Julie L. Christensen ₁ , Irving L. Weissman ₁

Affiliation

c-kit（+）（K）谱系（-/ lo）（L）Sca-1（+）（S）造血细胞群中包含具有克隆能力的多能小鼠造血干细胞（HSC）和祖细胞；长期（LT）和短期（ST）HSC为Thy-1.1（lo）。c-kit是受体酪氨酸激酶家族的成员，酪氨酸激酶家族是在造血细胞增殖和分化中起重要作用的一类受体。为了确定Flk-2 / Flt3受体酪氨酸激酶是否在最原始的LT-HSC上表达，我们根据Flk-2表面表达对高度纯化的多能干细胞和祖细胞进行了分类，并将其用于竞争性重组分析。Flk-2（-）HSC的数量较少，导致大多数接受者的长期多系重组，而Flk-2（+）多能细胞的转移主要导致短期多系重构。分析成年小鼠骨髓的KLS亚群的Flk-2和Thy-1.1表达。分离了三个表型和功能上不同的种群：Thy（lo）Flk-2（-）（LT-HSCs），Thy（lo）Flk-2（+）（ST-HSCs）和Thy（-）Flk-2（ +）多能祖细胞。Thy-1.1的丧失和Flk-2表达的增加标志着HSC成熟中自我更新的丧失。在谱系混合物中添加Flk-2抗体可从成年骨髓中直接分离LT-HSC，如从许多小鼠品系中获得c-kit（+）lin（-）Sca-1（+）Flk-2（-）。胎儿肝脏HSC包含在Flk-2（-）和Flk-2（+）KTLS细胞中。分离了三个表型和功能上不同的种群：Thy（lo）Flk-2（-）（LT-HSCs），Thy（lo）Flk-2（+）（ST-HSCs）和Thy（-）Flk-2（ +）多能祖细胞。Thy-1.1的丧失和Flk-2表达的增加标志着HSC成熟中自我更新的丧失。在谱系混合物中添加Flk-2抗体可从成年骨髓中直接分离LT-HSC，如从许多小鼠品系中获得c-kit（+）lin（-）Sca-1（+）Flk-2（-）。胎儿肝脏HSC包含在Flk-2（-）和Flk-2（+）KTLS细胞中。分离了三个表型和功能上不同的种群：Thy（lo）Flk-2（-）（LT-HSCs），Thy（lo）Flk-2（+）（ST-HSCs）和Thy（-）Flk-2（ +）多能祖细胞。Thy-1.1的丧失和Flk-2表达的增加标志着HSC成熟中自我更新的丧失。向谱系混合物中添加Flk-2抗体可从成年骨髓中直接分离LT-HSC，如从许多小鼠品系中获得c-kit（+）lin（-）Sca-1（+）Flk-2（-）。胎儿肝脏HSC包含在Flk-2（-）和Flk-2（+）KTLS细胞中。在谱系混合物中添加Flk-2抗体可从成年骨髓中直接分离LT-HSC，如从许多小鼠品系中获得c-kit（+）lin（-）Sca-1（+）Flk-2（-）。胎儿肝脏HSC包含在Flk-2（-）和Flk-2（+）KTLS细胞中。在谱系混合物中添加Flk-2抗体可从成年骨髓中直接分离LT-HSC，如从许多小鼠品系中获得c-kit（+）lin（-）Sca-1（+）Flk-2（-）。胎儿肝脏HSC包含在Flk-2（-）和Flk-2（+）KTLS细胞中。

"点击查看英文标题和摘要"

Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells.

Clonogenic multipotent mouse hematopoietic stem cells (HSCs) and progenitor cells are contained within the c-kit(+) (K) lineage(-/lo) (L) Sca-1(+) (S) population of hematopoietic cells; long-term (LT) and short-term (ST) HSCs are Thy-1.1(lo). c-kit is a member of the receptor tyrosine kinase family, a class of receptors that are important in the proliferation and differentiation of hematopoietic cells. To establish whether the Flk-2/Flt3 receptor tyrosine kinase was expressed on the most primitive LT-HSCs, we sorted highly purified multipotent stem and progenitor cells on the basis of Flk-2 surface expression and used them in competitive reconstitution assays. Low numbers of Flk-2(-) HSCs gave rise to long-term multilineage reconstitution in the majority of recipients, whereas the transfer of Flk-2(+) multipotent cells resulted in mostly short-term multilineage reconstitution. The KLS subset of adult mouse bone marrow was analyzed for Flk-2 and Thy-1.1 expression. Three phenotypically and functionally distinct populations were isolated: Thy(lo) Flk-2(-) (LT-HSCs), Thy(lo) Flk-2(+) (ST-HSCs), and Thy(-) Flk-2(+) multipotent progenitors. The loss of Thy-1.1 and gain of Flk-2 expression marks the loss of self-renewal in HSC maturation. The addition of Flk-2 antibody to the lineage mix allows direct isolation of LT-HSC from adult bone marrow as c-kit(+) lin(-) Sca-1(+) Flk-2(-) from many strains of mice. Fetal liver HSCs are contained within Flk-2(-) and Flk-2(+) KTLS cells.

更新日期：2017-01-31

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南