Characterization of Cre recombinase activity for in vivo targeting of adipocyte precursor cells.

Characterization of Cre recombinase activity for in vivo targeting of adipocyte precursor cells.
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CRE重组酶活性的表征是脂肪细胞前体细胞的体内靶向。

DOI:
10.1016/j.stemcr.2014.10.009
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发表时间:
2014-12-09
期刊:
影响因子:
5.9
通讯作者:
Feldman, Brian J.
Feldman, Brian J.
中科院分区:
医学1区
文献类型:
--
作者:
Krueger, Katherine C.;Costa, Maria Jose;Du, Hongqing;Feldman, Brian J.

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肥胖和代谢性疾病发病率的增加强调了阐明脂肪组织发育生物学的重要性。最近发现的用于体内脂肪前体细胞(APCs)前瞻性鉴定的细胞表面标记物将极大地促进这些研究,但在体内特异性靶向这些细胞的工具尚未确定。在这里,我们调查了三种转基因小鼠系,Fabp4-Cre, PdgfRα-Cre和Prx1-Cre,精确评估cre介导的脂肪基质群体和成熟组织中的重组。我们的数据为这些工具在脂肪组织中调节基因表达的效用提供了关键的见解。特别是,Fabp4-Cre对apc无效,其活性也不局限于这些细胞。PdgfRα-Cre在绝大多数apc中指导重组,但也针对其他人群。相比之下,Prx1-Cre的脂肪表达主要局限于皮下腹股沟APC,这将为解剖脂肪库中APC的功能提供价值。流式细胞术评估体内靶向脂肪前体的遗传工具Fabp4-Cre仅在一小部分白色脂肪前体中有活性PdgfRα-Cre在几乎所有白色和棕色脂肪前体中都有活性在脂肪组织中,Prx1-Cre活性仅限于皮下腹股沟前体。在这里,Krueger等人使用这些标记调查了几种转基因小鼠系脂肪库中cre介导的重组。这些数据为这些工具在脂肪组织中调节基因表达的适用性提供了关键的见解。
The increased incidence of obesity and metabolic disease underscores the importance of elucidating the biology of adipose tissue development. The recent discovery of cell surface markers for prospective identification of adipose precursor cells (APCs) in vivo will greatly facilitate these studies, yet tools for specifically targeting these cells in vivo have not been identified. Here, we survey three transgenic mouse lines, Fabp4-Cre, PdgfRα-Cre, and Prx1-Cre, precisely assessing Cre-mediated recombination in adipose stromal populations and mature tissues. Our data provide key insights into the utility of these tools to modulate gene expression in adipose tissues. In particular, Fabp4-Cre is not effective to target APCs, nor is its activity restricted to these cells. PdgfRα-Cre directs recombination in the vast majority of APCs, but also targets other populations. In contrast, adipose expression of Prx1-Cre is chiefly limited to subcutaneous inguinal APCs, which will be valuable for dissection of APC functions among adipose depots. Genetic tools to target adipose precursors in vivo assessed by flow cytometry Fabp4-Cre is active only in a small subset of white adipose precursors PdgfRα-Cre is active in nearly all white and brown adipose precursors In adipose tissue, Prx1-Cre activity is limited to subcutaneous inguinal precursors The discovery of cell surface markers that label adipose progenitors identifies new avenues of stem cell and metabolic research. Here, Krueger et al. use these markers to survey Cre-mediated recombination in the adipose depots of several transgenic mouse lines. These data provide key insights into the suitability of these tools to modulate gene expression in adipose tissues.
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