Lineage specification of Flk-1+ progenitors is associated with divergent Sox7 expression in cardiopoiesis.
Lineage specification of Flk-1+ progenitors is associated with divergent Sox7 expression in cardiopoiesis.
复制标题
DOI：
10.1016/j.diff.2008.10.012
复制
发表时间：
2009-03
期刊：
影响因子：
2.9
通讯作者：
Terzic, Andre
中科院分区：
文献类型：
--
作者：
Nelson, Timothy J.;Chiriac, Anca;Faustino, Randolph S.;Crespo-Diaz, Ruben J.;Behfar, Atta;Terzic, Andre
胚胎干细胞分化概括了发育胚胎的不同表型，可根据谱系说明的标记进行追踪。在原肠胚形成时，血管内皮生长因子（VEGF）受体Flk-1 （KDR）识别出胚胎干细胞的中胚层限制性潜能。Flk-1+祖细胞的多谱系倾向要求绘制改变命运的辅助因子，以便对分化的细胞类型进行分层和预测谱系能力。在这里，基于Flk-1的早期胚胎干细胞后代选择分离了一个缺乏多能性（Oct4, Sox2）和内胚层（Sox17）标记的群体。Flk-1+群体的基因表达谱显示，血管源性Sox7转录因子显著上调，这与原始心脏转录因子GATA-4、心肌蛋白和Nkx2.5的出现重叠。用趋化因子受体CXCR4对亲代Flk-1+库进行分类，以丰富心脏生成亚群，发现Sox7的表达存在差异，与心脏祖细胞相比，非心脏祖细胞的Sox7表达增加了7倍。生物信息学分辨率分离了Sox转录因子家族成员与Flk-1/CXCR4轴之间的框架基因表达关系，并显著整合了β-catenin信号传导。因此，Sox7基因的差异表达呈现出一种新的生物标记谱，以及可能的调节开关，以区分Flk-1+多谱系祖细胞中的心血管谱系。
Embryonic stem cell differentiation recapitulates the diverse phenotypes of a developing embryo, traceable according to markers of lineage specification. At gastrulation, the vascular endothelial growth factor (VEGF) receptor, Flk-1 (KDR), identifies a mesoderm-restricted potential of embryonic stem cells. The multi-lineage propensity of Flk-1+ progenitors mandates the mapping of fate-modifying co-factors in order to stratify differentiating cytotypes and predict lineage competency. Here, Flk-1 based selection of early embryonic stem cell progeny separated a population depleted of pluripotent (Oct4, Sox2) and endoderm (Sox17) markers. The gene expression profile of the Flk-1+ population was notable for a significant upregulation in the vasculogenic Sox7 transcription factor, which overlapped with the emergence of primordial cardiac transcription factors GATA-4, Myocardin and Nkx2.5. Sorting the parental Flk-1+ pool with the chemokine receptor CXCR4 to enrich the cardiopoietic subpopulation uncovered divergent Sox7 expression, with a 7-fold induction in non-cardiac compared to cardiac progenitors. Bioinformatic resolution sequestered a framework gene expression relationships between Sox transcription factor family members and the Flk-1/CXCR4 axes with significant integration of β-catenin signaling. Thus, differential Sox7 gene expression presents a novel biomarker profile, and possible regulatory switch, to distinguish cardiovascular pedigrees within Flk-1+ multi-lineage progenitors.
登录
查看更多内容
DOI：
10.1084/jem.20061916
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Behfar A;Perez-Terzic C;Faustino RS;Arrell DK;Hodgson DM;Yamada S;Puceat M;Niederländer N;Alekseev AE;Zingman LV;Terzic A
通讯作者：
Terzic A
影响因子：
5.2
作者：
Arrell, D. Kent;Niederlaender, Nicolas J.;Terzic, Andre
通讯作者：
Terzic, Andre
DOI：
10.1152/ajpheart.00363.2005
发表时间：
2006-10-01
影响因子：
4.8
作者：
Chen, Yu;Amende, Ivo;Morgan, James P.
通讯作者：
Morgan, James P.
DOI：
10.1084/jem.20061469
发表时间：
2006-10-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kolossov E;Bostani T;Roell W;Breitbach M;Pillekamp F;Nygren JM;Sasse P;Rubenchik O;Fries JW;Wenzel D;Geisen C;Xia Y;Lu Z;Duan Y;Kettenhofen R;Jovinge S;Bloch W;Bohlen H;Welz A;Hescheler J;Jacobsen SE;Fleischmann BK
通讯作者：
Fleischmann BK
DOI：
10.1073/pnas.0605768103
发表时间：
2006-12-26
影响因子：
11.1
作者：
Naito, Atsuhiko T.;Shiojima, Ichiro;Komuro, Issei
通讯作者：
Komuro, Issei