SOX2, OCT3/4 and NANOG expression and cellular plasticity in rare human somatic cells requires CD73.
SOX2, OCT3/4 and NANOG expression and cellular plasticity in rare human somatic cells requires CD73.
复制标题
稀有人类体细胞中 SOX2、OCT3/4 和 NANOG 的表达和细胞可塑性需要 CD73。
DOI：
10.1016/j.cellsig.2016.09.008
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发表时间：
2016
影响因子：
4.8
通讯作者：
Tlsty,TheaD
中科院分区：
文献类型：
--
作者：
Pan,Deng;Roy,Somdutta;Gascard,Philippe;Zhao,Jianxin;Chen-Tanyolac,Chira;Tlsty,TheaD
从成人组织分离的内源性塑料体细胞(EPS)在体外和体内都表现出广泛的谱系可塑性。在这里，我们通过免疫组织化学分析先前发现的EPS特异性生物标记物(CD73+、EPCAM+和CD90−)，在未患病的乳腺标本中观察到这些罕见的EPS细胞处于潜伏状态，即缺乏SOX2、Oct3/4和NANOG(SON)的表达。我们还报道了一种新的机制，这些潜伏的EPS细胞在体外获得SON表达和可塑性。4种细胞外因子是EPS细胞获得SON表达和谱系可塑性所必需的：腺苷(由5‘外核苷酸酶CD73产生，并通过腺苷受体ADORA2b激活依赖于PKA的IL6/STAT3通路)、IL6、FGF2和激活素A。阻断任何途径成分都会使EPS细胞不能表达SON和谱系可塑性。值得注意的是，hESCs不使用腺苷或IL6，也不表达CD73或ADORA2b，抑制腺苷信号并不会削弱它们的可塑性。因此，这里提供的数据描绘了在罕见的、未分化的人类细胞中访问SON表达的新电路和生理信号。
Endogenous Plastic Somatic (ePS) cells isolated from adult human tissues exhibit extensive lineage plasticityin vitroandin vivo. Here we visualize these rare ePS cells in a latent state,i.e.lacking SOX2, OCT3/4 and NANOG (SON) expression, in non-diseased breast specimens through immunohistochemical analysis of previously identified ePS-specific biomarkers (CD73+, EpCAM+and CD90−). We also report a novel mechanism by which these latent ePS cells acquire SON expression and plasticityin vitro. Four extracellular factors are necessary for the acquisition of SON expression and lineage plasticity in ePS cells: adenosine (which is produced by the 5′ ecto-nucleotidase CD73 and activates in turn the PKA-dependent IL6/STAT3 pathway through the adenosine receptor ADORA2b), IL6, FGF2 and ACTIVIN A. Blocking any pathway component renders ePS cells incapable of SON expression and lineage plasticity. Notably, hESCs do not use adenosine or IL6 nor they express CD73 or ADORA2b and inhibition of adenosine signaling does not ablate their plasticity. Therefore, the data presented here delineate novel circuitry and physiological signals for accessing SON expression in rare, undifferentiated human cells.