Ghent Fertility and Stem Cell Team (G-FAST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium.
Ghent Fertility and Stem Cell Team (G-FAST), Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, Ghent 9000, Belgium Present address: Coastal Fertility Specialists, 1375 Hospital Drive, Mt Pleasant, SC 29464, USA.
Hum Reprod Update. 2015 Sep-Oct;21(5):616-26. doi: 10.1093/humupd/dmv028. Epub 2015 Jun 18.
Until recently, the temporal events that precede the generation of pluripotent embryonic stem cells (ESCs) and their equivalence with specific developmental stages in vivo was poorly understood. Our group has discovered the existence of a transient epiblast-like structure, coined the post-inner cell mass (ICM) intermediate or PICMI, that emerges before human ESC (hESCs) are established, which supports their primed nature (i.e. already showing some predispositions towards certain cell types) of pluripotency.
The PICMI results from the progressive epithelialization of the ICM and it expresses a mixture of early and late epiblast markers, as well as some primordial germ cell markers. The PICMI is a closer progenitor of hESCs than the ICM and it can be seen as the first proof of why all existing hESCs, until recently, display a primed state of pluripotency.
Even though the pluripotent characteristics of ESCs differ from mouse (naïve) to human (primed), it has recently been shown in mice that a similar process of self-organization at the transition from ICM to (naïve) mouse ESCs (mESCs) transforms the amorphous ICM into a rosette of polarized epiblast cells, a mouse PICMI. The transient PICMI stage is therefore at the origin of both mESCs and hESCs. In addition, several groups have now reported the conversion from primed to the naïve (mESCs-like) hESCs, broadening the pluripotency spectrum and opening new opportunities for the use of pluripotent stem cells.
In this review, we discuss the recent discoveries of mouse and human transient states from ICM to ESCs and their relation towards the state of pluripotency in the eventual stem cells, being naïve or primed. We will now further investigate how these intermediate and/or different pluripotent stages may impact the use of human stem cells in regenerative medicine and assisted reproductive technology.
直到最近，人们对多能胚胎干细胞（ESCs）生成之前的时间事件及其与体内特定发育阶段的等价性仍知之甚少。我们的研究小组发现了一种短暂的胚外样结构的存在，将其命名为原内层细胞团（ICM）后中间体或 PICMI，它出现在人类胚胎干细胞（hESCs）建立之前，支持其初始状态（即已经表现出对某些细胞类型的某些倾向性）的多能性。
PICMI 源自 ICM 的逐渐上皮化，它表达了早期和晚期胚外样标志物的混合物，以及一些原始生殖细胞标志物。PICMI 是 hESC 的更接近的祖细胞，它可以被视为为什么所有现有的 hESC 直到最近都显示出初始多能状态的第一个证据。
尽管 ESCs 的多能特性在小鼠（原始）和人类（初始）之间存在差异，但最近在小鼠中已经表明，在从 ICM 到（原始）小鼠 ESCs（mESCs）的过渡中，类似的自我组织过程将无定形的 ICM 转化为极化的胚外细胞的玫瑰花结，即小鼠 PICMI。因此，短暂的 PICMI 阶段是 mESCs 和 hESCs 的起源。此外，现在有几个小组已经报道了从初始状态到原始（mESCs 样）hESC 的转化，拓宽了多能性谱，并为多能干细胞的应用开辟了新的机会。
在这篇综述中，我们讨论了从 ICM 到 ESCs 的小鼠和人类短暂状态的最新发现及其与最终干细胞多能性状态的关系，无论是原始状态还是初始状态。我们将进一步研究这些中间和/或不同的多能阶段如何影响人类干细胞在再生医学和辅助生殖技术中的应用。
