Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation
Aggregation of embryonic stem cells induces Nanog repression and primitive endoderm differentiation
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DOI：
10.1242/jcs.01489
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发表时间：
2004-11-01
影响因子：
4
通讯作者：
Terada, N
中科院分区：
文献类型：
--
作者：
Hamazaki, T;Oka, M;Terada, N
当允许胚胎干细胞聚集时，聚集球体的外层（称为胚状体）分化成原始内胚层。这种细胞谱系的初始特化促进了胚状体内部物质的进一步分化。这些过程被认为是从胚泡阶段到卵柱阶段的早期胚胎发育的重演。在白血病抑制因子/STAT 3和血清/BMP 4的存在下，胚状体中原始内胚层的形成仅由胚胎干细胞的聚集诱导，这被认为足以实现胚胎干细胞的自我更新。有趣的是，细胞聚集本身在外层诱导Nanog阻遏，这是聚集诱导的原始内胚层形成所必需的。这些数据说明了在早期胚胎发育过程中基于聚集的细胞命运特化，此时Nanog的下调起着至关重要的作用。
When embryonic stem cells are allowed to aggregate, the outer layer of the aggregated spheres (referred to as embryoid bodies) differentiates into primitive endoderm. This initial specification of cell lineage facilitates further differentiation of the inner mass of the embryoid bodies. These processes are considered to recapitulate early embryonic development from the blastocyst stage to the egg-cylinder stage. Formation of the primitive endoderm layer in the embryoid bodies was induced solely by aggregation of embryonic stem cells, in the presence of leukemia inhibitory factor/STAT3 and serum/BMP4, which were considered to be sufficient for embryonic stem cell self-renewal. Interestingly, cell aggregation by itself induced Nanog repression at the outer layer, which was essential for aggregation-induced primitive endoderm formation. These data illustrate aggregation-based cell-fate specification during early embryonic development, when downregulation of Nanog plays a crucial role.