Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers

Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers
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DOI:
10.1634/stemcells.2004-0279
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发表时间:
2005-04-01
期刊:
影响因子:
5.2
通讯作者:
Hayek, A
Hayek, A
中科院分区:
医学2区
文献类型:
--
作者:
Beattie, GM;Lopez, AD;Hayek, A

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到目前为止,所有可用于研究的人类胚胎干细胞(HESCs)都需要从饲养层分泌未知的可溶性因子来维持未分化状态和多能性。白血病抑制因子激活STAT3是维持小鼠胚胎干细胞“干性”所必需的,但在人类胚胎干细胞中并不需要,这表明在人类细胞中存在着自我更新和多能性的替代信号通路。在这里,我们证明激活素A是由小鼠胚胎饲养层(MEFS)分泌的,并且富含激活素A的培养液能够在不需要饲养层、mEFS的条件培养液或STAT3激活的情况下维持20代hESCs的未分化状态。体内的畸胎瘤形成表明,hESCs既保留了正常的核型,又保留了未分化细胞的标记,包括Oct-4、Nanog和TRA-1-60,并保持了多能性。
To date, all human embryonic stem cells (hESCs) available for research require unidentified soluble factors secreted from feeder layers to maintain the undifferentiated state and pluripotency. Activation of STAT3 by leukemia inhibitory factor is required to maintain "stemness" in mouse embryonic stem cells, but not in hESCs, suggesting the existence of alternate signaling pathways for self-renewal and pluripotency in human cells. Here we show that activin A is secreted by mouse embryonic feeder layers (mEFs) and that culture medium enriched with activin A is capable of maintaining hESCs in the undifferentiated state for > 20 passages without the need for feeder layers, conditioned medium from mEFs, or STAT3 activation. hESCs retained both normal karyotype and markers of undifferentiated cells, including Oct-4, nanog, and TRA-1-60 and remained pluripotent, as shown by the in vivo formation of teratomas.