OSKM Induce Extraembryonic Endoderm Stem Cells in Parallel to Induced Pluripotent Stem Cells.
OSKM Induce Extraembryonic Endoderm Stem Cells in Parallel to Induced Pluripotent Stem Cells.
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DOI：
10.1016/j.stemcr.2016.02.003
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发表时间：
2016-04-12
影响因子：
5.9
通讯作者：
Ralston A
中科院分区：
文献类型：
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作者：
Parenti A;Halbisen MA;Wang K;Latham K;Ralston A
重编程因子 OCT4、SOX2、KLF4 和 MYC (OSKM) 可以重新激活终末分化细胞中的多能性网络，但也可以调节其他环境（例如小鼠原始内胚层）中非多能性基因的表达。原始内胚层是与囊胚中的多能外胚层平行建立的胚外谱系，并且是胚外内胚层干（XEN）细胞的祖细胞库。我们发现 OSKM 诱导内胚层基因表达，导致诱导 XEN (iXEN) 细胞的形成，该细胞具有囊胚来源的 XEN 细胞的关键特性，包括形态、转录谱、自我更新和多能性。我们的数据显示 iXEN 细胞与诱导多能干细胞平行出现，表明 OSKM 在重编程过程中驱动细胞走向两种不同的细胞命运。 OSKM 在小鼠成纤维细胞中诱导胚胎外内胚层干细胞 (iXENC) iPSC 不通过 iXEN 中间体转变 iXENC 源自成纤维细胞，与 iPSC 平行。内胚层基因调节选择成为 iXENC 或 iPSC Parenti 及其同事确定了在小鼠成纤维细胞中过度表达 OSKM 诱导的第二种干细胞类型。作者利用谱系追踪表明，诱导胚胎外内胚层干细胞 (iXEN) 与诱导多能干细胞 (iPSC) 平行出现，这与据报道在化学重编程过程中充当成纤维细胞和 iPSC 之间中间体的类 XEN 状态形成鲜明对比。
The reprogramming factors OCT4, SOX2, KLF4, and MYC (OSKM) can reactivate the pluripotency network in terminally differentiated cells, but also regulate expression of non-pluripotency genes in other contexts, such as the mouse primitive endoderm. The primitive endoderm is an extraembryonic lineage established in parallel to the pluripotent epiblast in the blastocyst, and is the progenitor pool for extraembryonic endoderm stem (XEN) cells. We show that OSKM induce expression of endodermal genes, leading to formation of induced XEN (iXEN) cells, which possess key properties of blastocyst-derived XEN cells, including morphology, transcription profile, self-renewal, and multipotency. Our data show that iXEN cells arise in parallel to induced pluripotent stem cells, indicating that OSKM drive cells to two distinct cell fates during reprogramming. OSKM induce extraembryonic endoderm stem cells (iXENCs) in mouse fibroblasts iPSCs do not transition through an iXEN intermediate iXENCs are derived from fibroblasts in parallel to iPSCs Endodermal genes regulate the choice to become iXENCs or iPSCs Parenti and colleagues identify a second stem cell type induced by overexpression of OSKM in mouse fibroblasts. Using lineage tracing, the authors show that induced extraembryonic endoderm stem (iXEN) cells arise in parallel to induced pluripotent stem cells (iPSCs), in stark contrast to the XEN-like state reported to serve as an intermediate between fibroblasts and iPSCs during chemical reprogramming.