Targeting of Mesenchymal Stromal Cells by Cre-Recombinase Transgenes Commonly Used to Target Osteoblast Lineage Cells.
Targeting of Mesenchymal Stromal Cells by Cre-Recombinase Transgenes Commonly Used to Target Osteoblast Lineage Cells.
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DOI：
10.1002/jbmr.2877
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Link DC
中科院分区：
文献类型：
--
作者：
Zhang J;Link DC
组织特异性Cre重组酶转基因的靶向特异性是解释与其使用相关的表型的关键。Ocn-Cre和Dmp 1-Cre转基因分别被广泛用于靶向成骨细胞和骨细胞。在这里，我们使用骨切片的高分辨率显微镜和流式细胞术来仔细定义这些转基因的靶向特异性。将这些转基因与Cxcl 12 gfp小鼠杂交以鉴定Cxcl 12丰富的网状（CAR）细胞，其是涉及造血干/祖细胞维持的血管周围间充质基质群体。我们发现，除了成骨细胞，Ocn-Cre靶向大多数CAR细胞和小动脉周细胞。令人惊讶的是，Dmp 1-Cre还靶向CAR细胞的一个子集，其中成骨细胞谱系基因的表达富集。最后，我们介绍了一种新的组织特异性Cre重组酶，Tagln-Cre，它有效地靶向成骨细胞，大多数CAR细胞，静脉窦和小动脉周细胞。这些数据表明，Ocn-Cre和Dmp 1-Cre靶向更广泛的基质细胞群体比以前认识到，并可能有助于设计未来的研究。此外，这些数据突出了骨髓间充质基质细胞的异质性，并提供了询问这种异质性的工具。
The targeting specificity of tissue-specific Cre-recombinase transgenes is a key to interpreting phenotypes associated with their use. The Ocn-Cre and Dmp1-Cre transgenes are widely used to target osteoblasts and osteocytes, respectively. Here, we used high-resolution microscopy of bone sections and flow cytometry to carefully define the targeting specificity of these transgenes. These transgenes were crossed with Cxcl12gfp mice to identify Cxcl12-abundant reticular (CAR) cells, which are a perivascular mesenchymal stromal population implicated in hematopoietic stem/progenitor cell maintenance. We show that in addition to osteoblasts, Ocn-Cre targets a majority of CAR cells and arteriolar pericytes. Surprisingly, Dmp1-Cre also targets a subset of CAR cells, in which expression of osteoblast-lineage genes is enriched. Finally, we introduce a new tissue-specific Cre-recombinase, Tagln-Cre, which efficiently targets osteoblasts, a majority of CAR cells, and both venous sinusoidal and arteriolar pericytes. These data show that Ocn-Cre and Dmp1-Cre target broader stromal cell populations than previously appreciated and may aid in the design of future studies. Moreover, these data highlight the heterogeneity of mesenchymal stromal cells in the bone marrow and provide tools to interrogate this heterogeneity.
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DOI：
10.1242/dev.017863
发表时间：
2008-09
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
El-Bizri N;Guignabert C;Wang L;Cheng A;Stankunas K;Chang CP;Mishina Y;Rabinovitch M
通讯作者：
Rabinovitch M
影响因子：
64.8
作者：
Inra CN;Zhou BO;Acar M;Murphy MM;Richardson J;Zhao Z;Morrison SJ
通讯作者：
Morrison SJ
影响因子：
4.1
作者：
Kalajzic, Ivo;Matthews, Brya G.;Torreggiani, Elena;Harris, Marie A.;Pajevic, Paola Divieti;Harris, Stephen E.
通讯作者：
Harris, Stephen E.
影响因子：
15.9
作者：
Eash, Kyle J.;Greenbaum, Adam M.;Link, Daniel C.
通讯作者：
Link, Daniel C.
影响因子：
32.4
作者：
Omatsu, Yoshiki;Sugiyama, Tatsuki;Nagasawa, Takashi
通讯作者：
Nagasawa, Takashi