Long-term self-renewal and directed differentiation of human embryonic stem cells in chemically defined conditions
Long-term self-renewal and directed differentiation of human embryonic stem cells in chemically defined conditions
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DOI：
10.1073/pnas.0602280103
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发表时间：
2006-05-02
影响因子：
11.1
通讯作者：
Ding, S
中科院分区：
文献类型：
--
作者：
Yao, S;Chen, S;Ding, S
控制人胚胎干细胞(HESC)命运的化学定义培养液(CDM)条件不仅有利于hESCs在研究和治疗中的实际应用，而且还为研究hESCs自我更新和分化的分子机制提供了一个良好的系统，而不需要与饲养层细胞和血清相关的多种未知和可变因素。在这里，我们报道了一种简单的CDM，它支持生长在Matrigel涂层表面上的hESCs在多个通道上高效的自我更新。在此条件下扩增的hESCs保持了多种hESC特异性标志物的表达，保持了hESC特有的形态，在体外具有正常的核型，并在体内发展为畸胎瘤。此外，在我们的CDM条件下，发现几种生长因子选择性地诱导培养的hESC分别向神经细胞、终止性内胚层/胰腺细胞和早期心肌细胞分化。因此，这种CDM条件为进一步表征hESC的自我更新和定向分化以及开发新的治疗方法提供了基础平台。
Chemically defined medium (CDM) conditions for controlling human embryonic stem cell (hESC) fate will not only facilitate the practical application of hESCs in research and therapy but also provide an excellent system for studying the molecular mechanisms underlying self-renewal and differentiation, without the multiple unknown and variable factors associated with feeder cells and serum. Here we report a simple CDM that supports efficient self-renewal of hESCs grown on a Matrigel-coated surface over multiple passages. Expanded hESCs under such conditions maintain expression of multiple hESC-specific markers, retain the characteristic hESC morphology, possess a normal karyotype in vitro, as well as develop teratomas in vivo. Additionally, several growth factors were found to selectively induce monolayer differentiation of hESC cultures toward neural, definitive endoderm/pancreatic and early cardiac muscle cells, respectively, in our CDM conditions. Therefore, this CDM condition provides a basic platform for further characterization of hESC self-renewal and directed differentiation, as well as the development of novel therapies.