After the blastocyst stage, once an embryo implanted in endometrium (in case of rodent), the inner cell mass (ICM) of a fertilized embryo segregates into two layers: hypoblast and epiblast. The epiblast cells are the functional progenitors of soma and germ cells which later differentiate into three layers: definitive endoderm, mesoderm and ectoderm. Stem cells derived from epiblast are pluripotent. These cells are called epiblast-derived stem cells (EpiSC) and have several different cellular and molecular characteristics with Embryonic Stem Cells (ESC). Pluripotency in EpiSC is essentially different from that of embryonic stem cells. The pluripotency of EpiSC is primed pluripotency: primed to differentiate into specific cell lineages. Naïve pluripotent stem cells (e.g. ESC) and primed plur
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| - Epiblast-derived stem cell (en)
- エピブラスト幹細胞 (ja)
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| - エピブラスト幹細胞（えぴぶらすとかんさいぼう、エピ幹細胞、epiblast stem cell、epi-stem cell、EpiSC）は、マウス胚のを単離培養して樹立される幹細胞。マウスES細胞よりもヒトES細胞に近い性質を持つ。幹細胞研究の新たなツールとして期待され、様々な研究が行われている。 (ja)
- After the blastocyst stage, once an embryo implanted in endometrium (in case of rodent), the inner cell mass (ICM) of a fertilized embryo segregates into two layers: hypoblast and epiblast. The epiblast cells are the functional progenitors of soma and germ cells which later differentiate into three layers: definitive endoderm, mesoderm and ectoderm. Stem cells derived from epiblast are pluripotent. These cells are called epiblast-derived stem cells (EpiSC) and have several different cellular and molecular characteristics with Embryonic Stem Cells (ESC). Pluripotency in EpiSC is essentially different from that of embryonic stem cells. The pluripotency of EpiSC is primed pluripotency: primed to differentiate into specific cell lineages. Naïve pluripotent stem cells (e.g. ESC) and primed plur (en)
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| - After the blastocyst stage, once an embryo implanted in endometrium (in case of rodent), the inner cell mass (ICM) of a fertilized embryo segregates into two layers: hypoblast and epiblast. The epiblast cells are the functional progenitors of soma and germ cells which later differentiate into three layers: definitive endoderm, mesoderm and ectoderm. Stem cells derived from epiblast are pluripotent. These cells are called epiblast-derived stem cells (EpiSC) and have several different cellular and molecular characteristics with Embryonic Stem Cells (ESC). Pluripotency in EpiSC is essentially different from that of embryonic stem cells. The pluripotency of EpiSC is primed pluripotency: primed to differentiate into specific cell lineages. Naïve pluripotent stem cells (e.g. ESC) and primed pluripotent stem cells (e.g. EpiSC) not only sustain the ability to self-renew but also maintain the capacity to differentiate. Since the cell status is primed to differentiate in EpiSC, however, one copy of the X chromosome in XX cells (female cells) in EpiSC is silenced (XaXi). EpiSC is unable to colonize and is not available to be used to produce chimeras. Conversely, XX cells in ESC are both active and can produce chimera when inserted into a blastocyst. Both ESC and EpiSC induce teratoma when injected in the test animals (scid mice) which proves pluripotency. EpiSC display several distinctive characteristics distinct from ESC (table 1). The cellular status of human ESC (hESC) is similar to primed state mouse stem cells rather than Naïve state. Table 1. Comparison of Naïve and Primed pluripotent states Differentiating Naïve pluripotent Stem cells into primed pluripotent stem cells (e.g. adding activin and fibroblast growth factor (FGF) in the culture medium) can be accomplished but reprogramming of Primed cells into Naïve cells is more difficult. Several approaches to reprogramming EpiSC to achieve Naïve pluripotency have been applied. One of those methods is transfecting the primed pluripotent stem cell with a reprogramming factor, Klf4). The reversion back to the naive-state has also been achieved by suppressing the activity of the histone methyltransferase MLL1, also known as KMT2A. The inhibition of MLL1 via the small-molecule inhibitor MM-401 in EpiSC showed marked increase in alkaline phosphatase staining as well as upregulation of "naive" markers such as Rex1 and downregulation of "primed" markers such as FGF5. Moreover, beyond the potency-state comparison, MLL1 inhibition was also shown to reactivate the silenced X-chromosome which is typically deactivated in post-implantation epiblast stem cells, suggesting an epigenetic reversion back to a more ground-level, naive state. What's more, some EpiSCs affected by the MLL1 inhibition-induced reversion were able to contribute to germline-competent chimeras, which had been considered as one of the most major differences between ESCs and EpiSCs. (en)
- エピブラスト幹細胞（えぴぶらすとかんさいぼう、エピ幹細胞、epiblast stem cell、epi-stem cell、EpiSC）は、マウス胚のを単離培養して樹立される幹細胞。マウスES細胞よりもヒトES細胞に近い性質を持つ。幹細胞研究の新たなツールとして期待され、様々な研究が行われている。 (ja)
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