Generation of multipotential mesendodermal progenitors from mouse embryonic stem cells via sustained Wnt pathway activation
Generation of multipotential mesendodermal progenitors from mouse embryonic stem cells via sustained Wnt pathway activation
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DOI：
10.1074/jbc.m704287200
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发表时间：
2007-10-26
影响因子：
4.8
通讯作者：
Stanton, Lawrence W.
中科院分区：
文献类型：
--
作者：
Bakre, Manjiri Manohar;Hoi, Aina;Stanton, Lawrence W.
多能胚胎干细胞（ESC）能够分化为属于体内所有三个胚层的细胞类型，这使它们成为一个有趣而激烈的研究领域。低效的特异性分化和不需要的细胞类型的污染是在再生医学中使用ESC的主要问题。从ESC产生的谱系特异性祖细胞可用于规避该问题。我们在这里证明，在多个小鼠和人类胚胎干细胞中持续激活Wnt通路（使用Wnt 3A或糖原合成酶激酶3 β抑制剂）导致中/内胚层特异性分化。使用单层培养条件，我们通过持续的Wnt途径激活从小鼠胚胎干细胞中产生了多能“中内胚层祖细胞克隆”（MPC）。MPC表达增加水平的中/内胚层和中内胚层标记物，并在培养一年以上时表现出稳定的表型。与未分化的ESC相比，MPC具有增强的沿着内皮、心脏、血管平滑肌和骨骼谱系分化的潜力。总之，我们证明了Wnt通路的激活可以用于从ESC产生谱系特异性祖细胞，其可以进一步分化成所需的器官特异性细胞。
Pluripotent embryonic stem cells (ESCs) are capable of differentiating into cell types belonging to all three germ layers within the body, which makes them an interesting and intense field of research. Inefficient specific differentiation and contamination with unwanted cell types are the major issues in the use of ESCs in regenerative medicine. Lineage-specific progenitors generated from ESCs could be utilized to circumvent the issue. We demonstrate here that sustained activation of the Wnt pathway ( using Wnt3A or an inhibitor of glycogen synthase kinase 3 beta) in multiple mouse and human ESCs results in meso/endodermspecific differentiation. Using monolayer culture conditions, we have generated multipotential "mesendodermal progenitor clones" (MPC) from mouse ESCs by sustained Wnt pathway activation. MPCs express increased levels of meso/endodermal and mesendodermal markers and exhibit a stable phenotype in culture over a year. The MPCs have enhanced potential to differentiate along endothelial, cardiac, vascular smooth muscle, and skeletal lineages than undifferentiated ESCs. In conclusion, we demonstrate that the Wnt pathway activation can be utilized to generate lineage-specific progenitors from ESCs, which can be further differentiated into desired organ-specific cells.