VSELs Maintain their Pluripotency and Competence to Differentiate after Enhanced Ex Vivo Expansion.
VSELs Maintain their Pluripotency and Competence to Differentiate after Enhanced Ex Vivo Expansion.
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DOI：
10.1007/s12015-018-9821-1
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发表时间：
2018-08
影响因子：
4.8
通讯作者：
Hénon P
中科院分区：
文献类型：
--
作者：
Lahlil R;Scrofani M;Barbet R;Tancredi C;Aries A;Hénon P
非常小的胚胎样干细胞（VSELs）被称为成体多能干细胞的一个子集，能够分化为所有三个胚层。然而，它们的数量少和静止性限制了它们在细胞治疗中应用的可能性。在本研究中，我们首先描绘了来自人脐带血CD34+细胞的不同血管血管亚群，以确定其纯度。接下来，我们在稳态条件下测定表达多能标记物NANOG的血管内皮细胞和对照细胞的全转录组基因表达水平。我们发现血管内皮细胞中有超过1000个基因下调，还有许多膜受体、细胞信号分子和CDKs mrna。此外，我们在胚胎干细胞（ESCs）中观察到一些多能性基因表达水平的不一致，这可能解释了血管内皮细胞的静止。然后，我们评估血管内皮细胞在特定和适当的培养基中扩展和分化的能力。在含有嘧啶吲哚衍生物（UM171）的特定培养基中培养12天后，血管内皮细胞首次在没有饲养细胞的情况下显著扩增，并重要地保持了向造血细胞和内皮细胞分化的能力。有趣的是，这种对血管内皮细胞自我更新的刺激恢复了一些下调基因的表达，这些基因被称为细胞增殖和分化的关键调节因子。这种多能扩增细胞的特性使其成为再生医学的潜在候选者。本文的在线版本（10.1007/s12015-018-9821-1）包含补充内容，仅供授权用户使用。
The very small embryonic-like stem cells (VSELs) are known as a subset of adult pluripotent stem cells able to differentiate to all three germ layers. However, their small number and quiescence restrict the possibility of their use in cell therapy. In the present study, we first delineate different subpopulation of VSELs from human cord blood CD34+ cells to define their purity. We next determine genes expression levels in the whole transcriptome of VSELs expressing the pluripotent marker NANOG and control cells under the steady state condition. We found that more than a thousand of genes are downregulated in VSELs, as well as many membrane receptors, cells signaling molecules and CDKs mRNAs. In addition, we observed discordance in some pluripotent genes expression levels with embryonic stem cells (ESCs), which could explain VSELs quiescence. We then evaluate VSELs capacity to expand and differentiate in vitro in specific and appropriate media. After 12 days culture in specific medium containing a pyrimidoindole derivative (UM171), VSELs were significantly expanded for the first time without feeder cells and importantly preserve their capacities to differentiate into hematopoietic and endothelial cells. Interestingly, this stimulation of VSELs self-renewal restores the expression of some downregulated genes known as key regulators of cell proliferation and differentiation. The properties of such pluripotent expanded cells make them a potential candidate in regenerative medicine. The online version of this article (10.1007/s12015-018-9821-1) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Alvarez-Gonzalez C;Duggleby R;Vagaska B;Querol S;Gomez SG;Ferretti P;Madrigal A
通讯作者：
Madrigal A
影响因子：
4.8
作者：
Guerin, Coralie L.;Rossi, Elisa;Smadja, David M.
通讯作者：
Smadja, David M.
影响因子：
20.3
作者：
Fares, Iman;Chagraoui, Jalila;Sauvageau, Guy
通讯作者：
Sauvageau, Guy
影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.
DOI：
10.1126/science.1256337
发表时间：
2014-09-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fares I;Chagraoui J;Gareau Y;Gingras S;Ruel R;Mayotte N;Csaszar E;Knapp DJ;Miller P;Ngom M;Imren S;Roy DC;Watts KL;Kiem HP;Herrington R;Iscove NN;Humphries RK;Eaves CJ;Cohen S;Marinier A;Zandstra PW;Sauvageau G
通讯作者：
Sauvageau G