Embryonic stem cell-derived microvesicles induce gene expression changes in Müller cells of the retina.
Embryonic stem cell-derived microvesicles induce gene expression changes in Müller cells of the retina.
复制标题
DOI：
10.1371/journal.pone.0050417
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Farber DB
中科院分区：
文献类型：
--
作者：
Katsman D;Stackpole EJ;Domin DR;Farber DB
细胞来源的微泡（MV）是细胞间通讯的重要组成部分，含有mRNA、miRNA、蛋白质和脂质，可将其生物活性物质从亲本细胞转移到其他来源的细胞。我们研究了胚胎干细胞（ESMVs）释放的MV对视网膜祖细胞Müller细胞的影响。培养的人Müller细胞每48小时暴露于小鼠ESMVs，共9次处理。通过光学显微镜观察处理的细胞中的形态学变化，其作为个体异质细胞生长，与未处理的细胞的均匀的、纺锤形的粘附细胞片相比。ESMV转移到穆勒细胞胚胎干细胞（ESC）中，参与维持多能性的mRNA，包括Oct 4和Sox 2，以及290簇的miRNA，它们是ESC特异性细胞周期的重要调节因子。此外，EMV暴露诱导Müller细胞中内源性人Oct4 mRNA基础水平上调。ESMV处理与未处理的Müller细胞的mRNA和miRNA微阵列揭示了参与诱导多能性、细胞增殖、早期眼基因和对视网膜保护和重塑重要的基因的上调，以及参与分化和细胞周期停滞的抑制性和瘢痕相关基因和miRNA的下调。为了进一步表征EMV处理的Müller细胞的异质细胞群，通过免疫细胞化学将其视网膜细胞标志物的表达与未处理的对照细胞进行比较。无长突细胞、神经节细胞和视杆细胞的标记物在处理的Müller细胞中存在，但在对照Müller细胞中不存在。总之，我们的研究结果表明，ESM诱导其靶Müller细胞的去分化和多能性，这可能会开启早期视网膜分化程序。
Cell-derived microvesicles (MVs), recognized as important components of cell-cell communication, contain mRNAs, miRNAs, proteins and lipids and transfer their bioactive contents from parent cells to cells of other origins. We have studied the effect that MVs released from embryonic stem cells (ESMVs) have on retinal progenitor Müller cells. Cultured human Müller cells were exposed to mouse ESMVs every 48 hours for a total of 9 treatments. Morphological changes were observed by light microscopy in the treated cells, which grew as individual heterogeneous cells, compared to the uniform, spindle-like adherent cellular sheets of untreated cells. ESMVs transferred to Müller cells embryonic stem cell (ESC) mRNAs involved in the maintenance of pluripotency, including Oct4 and Sox2, and the miRNAs of the 290 cluster, important regulators of the ESC-specific cell cycle. Moreover, ESMV exposure induced up-regulation of the basal levels of endogenous human Oct4 mRNA in Müller cells. mRNA and miRNA microarrays of ESMV-treated vs. untreated Müller cells revealed the up-regulation of genes and miRNAs involved in the induction of pluripotency, cellular proliferation, early ocular genes and genes important for retinal protection and remodeling, as well as the down-regulation of inhibitory and scar-related genes and miRNAs involved in differentiation and cell cycle arrest. To further characterize the heterogeneous cell population of ESMV-treated Müller cells, their expression of retinal cell markers was compared to that in untreated control cells by immunocytochemistry. Markers for amacrine, ganglion and rod photoreceptors were present in treated but not in control Müller cells. Together, our findings indicate that ESMs induce de-differentiation and pluripotency in their target Müller cells, which may turn on an early retinogenic program of differentiation.
登录
查看更多内容
影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
3.7
作者：
Bruno S;Grange C;Collino F;Deregibus MC;Cantaluppi V;Biancone L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
5.3
作者：
Fausett, Blake V.;Gumerson, Jessica D.;Goldman, Daniel
通讯作者：
Goldman, Daniel
影响因子：
20.3
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
25
作者：
Fischer, AJ;Reh, TA
通讯作者：
Reh, TA