Long Noncoding RNA: Function and Mechanism on Differentiation of Mesenchymal Stem Cells and Embryonic Stem Cells

2019 ◽  
Vol 14 (3) ◽  
pp. 259-267
Author(s):  
Jian Zhu ◽  
Yitian Wang ◽  
Wei Yu ◽  
Kaishun Xia ◽  
Yuluan Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Transcription Regulation ◽  
Noncoding Rna ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Differentiation Process ◽  
Pathologic Process

Background:Long suspected as transcriptional noise, recently recognized, long non-coding RNAs (lncRNAs) are emerging as an indicator, biomarker and therapy target in the physiologic and pathologic process. Mesenchymal stem cells and embryonic stem cells are important source for normal and therapeutic tissue repair. However, the mechanism of stem cell differentiation is not completely understood. Research on lncRNAs may provide novel insights into the mechanism of differentiation process of the stem cell which is important for the application of stem cell therapy. The lncRNAs field is still very young, new insights into lncRNAs function are emerging to a greater understanding of biological processes. Objective: In this review, we summarize the recent researches studying lncRNAs and illustrate how they act in the differentiation of the mesenchymal stem cells and embryonic stem cells, and discuss some future directions in this field. Results: Numerous lncRNAs were differentially expressed during differentiation of mesenchymal stem cells and embryonic stem cells. LncRNAs were able to regulate the differentiation processes through epigenetic regulation, transcription regulation and post-transcription regulation. Conclusion: LncRNAs are involved in the differentiation process of mesenchymal stem cells and embryonic stem cells, and they could become promising indicator, biomarker and therapeutic targets in the physiologic and pathologic process. However, the mechanisms of the role of lncRNAs still require further investigation.

scholarly journals Functions of Circular RNAs in Regulating Adipogenesis of Mesenchymal Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Fanglin Wang ◽  
Xiang Li ◽  
Zhiyuan Li ◽  
Shoushuai Wang ◽  
Jun Fan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Circular Rna ◽  
Circular Rnas ◽  
Differentiation Process

The mesenchymal stem cells (MSCs) are known as highly plastic stem cells and can differentiate into specialized tissues such as adipose tissue, osseous tissue, muscle tissue, and nervous tissue. The differentiation of mesenchymal stem cells is very important in regenerative medicine. Their differentiation process is regulated by signaling pathways of epigenetic, transcriptional, and posttranscriptional levels. Circular RNA (circRNA), a class of noncoding RNAs generated from protein-coding genes, plays a pivotal regulatory role in many biological processes. Accumulated studies have demonstrated that several circRNAs participate in the cell differentiation process of mesenchymal stem cells in vitro and in vivo. In the current review, characteristics and functions of circRNAs in stem cell differentiation will be discussed. The mechanism and key role of circRNAs in regulating mesenchymal stem cell differentiation, especially adipogenesis, will be reviewed and discussed. Understanding the roles of these circRNAs will present us with a more comprehensive signal path network of modulating stem cell differentiation and help us discover potential biomarkers and therapeutic targets in clinic.

scholarly journals TGF-β Inhibitor SB431542 Promotes the Differentiation of Induced Pluripotent Stem Cells and Embryonic Stem Cells into Mesenchymal-Like Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Alessander Leyendecker Junior
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Markers ◽  
Induced Pluripotent

Due to their potential for tissue engineering applications and ability to modulate the immune system and reduce inflammation, mesenchymal stem cells (MSCs) have been explored as a promising option for the treatment of chronic diseases and injuries. However, there are problems associated with the use of this type of cell that limit their applications. Several studies have been exploring the possibility to produce mesenchymal stem cells from pluripotent stem cells (PSCs). The aim of these studies is to generate MSCs with advantageous characteristics of both PSCs and MSCs. However, there are still some questions concerning the characteristics of MSCs derived from the differentiation of PSCs that must be answered before they can be used to treat diseases and injuries. The objective of this study was, therefore, to determine if PSCs exposed to SB431542, a TGF-β inhibitor, are able to differentiate to MSCs, judging by morphology, expression of mesenchymal and pluripotent stem cell markers, expression of pluripotency-related genes, and ability to differentiate to osteocytes and adipocytes. The results obtained demonstrated that it is possible to induce the differentiation of both embryonic stem cells and induce pluripotent stem cells into cells with characteristics that highly resemble those from MSCs through the inhibition of the TGF-β pathway.

scholarly journals A basic guide to stem cell differentiation

2016 ◽  
Vol 215 (3) ◽  
pp. 293-293
Author(s):  
Ben Short
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cells ◽  
Intracellular Ph ◽  
Embryonic Stem ◽  
Stem Cell Differentiation

Increasing intracellular pH promotes the differentiation of adult and embryonic stem cells.

Regulated Expression of Activated Notch 1 during Embryonic Stem Cell Differentiation Preserves Multipotential Progenitors and Promotes Erythroid Cell Fate.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4151-4151
Author(s):  
Uma Ganapati ◽  
Lynne A. Bui ◽  
Maureen Lynch ◽  
Milana Dolezal ◽  
Hongying Tina Tan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Notch Signaling ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Erythroid Cell ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Stem

Abstract Hematopoietic stem cells pass sequentially through a series of developmental decision points regulating self-renewal and lineage-specific differentiation. In normal hematopoiesis proliferation is tightly linked to differentiation in ways that are poorly understood. The Notch gene family has been shown to be evolutionarily conserved and to play an important role in determining cell fate, survival, and proliferation in multiple organisms. Numerous in vitro and in vivo studies strongly support a role for Notch signaling in the regulation of stem cell signaling and hematopoiesis. To define the function of Notch in the earliest stages of hematopoiesis, a Tetracycline-inducible system regulating expression of a ligand-independent, constitutively active form of Notch1 was introduced into murine E14Tg2a embryonic stem cells. (Era and Witte, PNAS, 97;1737–1742,2000). During co-culture, OP9 stromal cells induce the embryonic stem cells to differentiate first to hemangioblasts and subsequently to hematopoietic cells. Our studies indicate that activation of Notch signaling in flk+ hemangioblasts dramatically reduces their proliferative capacity without inducing apoptosis. Furthermore, Notch1 activation significantly reduces the levels of hematopoietic stem cell markers CD34, c-Kit and the myeloid marker CD11b. These reversible effects suggest that Notch signaling maintains the hemangioblasts in an immature state and blocks hematopoietic differentiation. When activated Notch is induced in committed hematopoietic progenitors, a shift towards definitive erythroid differentiation and decreased myeloid differentiation is observed. Microarray analysis of day8 hematopoietic progenitors following Notch activation in hemangioblasts indicates upregulation of known downstream targets of Notch signaling. Based on these results, we propose that Notch signaling plays a critical role in the earliest events regulating hematopoiesis.

Oct4 and Its Pseudogenes Confuse Stem Cell Research.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3700-3700
Author(s):  
Stefanie Liedtke ◽  
Jürgen Enczmann ◽  
Simon Waclawczyk ◽  
Peter Wernet ◽  
Gesine Kögler
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Differentiated Cells ◽  
Alternatively Spliced

Abstract Octamer-binding transcription factor 4 (Oct4) encodes a nuclear protein that belongs to a family of transcription factors containing the POU DNA binding domain. It is specifically expressed in embryonic stem cells but can also be detected in adult stem cells such as bone marrow-derived mesenchymal stem cells. The expression of Oct4 is down-regulated coincident with stem cell differentiation and loss of expression leading to differentiation. It plays a critical role for maintaining pluripotency and self-renewal of embryonic stem cells. However, the usefulness of Oct4 as a pluripotency marker was challenged recently. More and more data seem to support that Oct4 is expressed on a variety of differentiated cells, including peripheral blood mononuclear cells. Taking into account that RT-PCR can potentially generate experimental artifacts due to pseudogene transcripts, the existence of Oct4 pseudogenes should be investigated further here. Suo et al. were able to detect transcription of some Oct4 pseudogenes in cancer cell lines as well as cancer tissues. These results show that some of the known Oct4 pseudogenes are transcribed in vivo and therefore could lead to RT-PCR artifacts. However this known problem was not seriously taken into consideration in recent publications on adult stem cells and tissue analysis referring to Oct4. We started with an initial alignment of Oct4 compared to its alternative splice variants as well as its pseudogenes. This alignment served as a prerequisite for an exact primer design. First the sequence and organization of the functional human Oct4 gene were clarified to allow comparison to the pseudogenes and alternatively spliced transcripts. The NCBI human EST database was searched and the UniGene cluster for Oct4 (NM_002701) examined. This yielded 13 mRNA sequences and 129 EST sequences. An additional BLASTn search of the human genome using single exons of Oct4 revealed several other highly similar sequences. All these hits encoded complete or partial Oct4 sequences and could therefore represent either functional members of an Oct4 gene family or pseudogenes. The fact that so many homologous sequences resemble the original Oct4 transcript makes an RT-PCR analysis difficult, because a lot of artifacts can arise during amplification. Therefore primers were designed which are able to exclude amplification of all unwanted transcripts. To conclude, based on the fact that the expression of Oct4 has been reported in adult stem cells as well as in a variety of differentiated cells the possibility cannot be excluded that the detected Oct4 signal came from alternatively spliced or Oct4 pseudogene transcripts. As shown here, an exact design of Oct4-specific primers is an inevitable prerequisite for appropriate RT-PCR analysis. In addition, a careful comparison of quantitative differences to human embryonic stem cells should be present too, before cells are described as embryonic like cells. We hope that our findings will help other stem cell researchers to find their appropriate tools especially for RT-PCR analysis and give an example how later problematic artifacts can be ruled out from the beginning by a detailed alignment as a prerequisite for designing appropriate primers.

Oct4 expression revisited: potential pitfalls for data misinterpretation in stem cell research

2008 ◽  
Vol 389 (7) ◽  
Author(s):  
Stefanie Liedtke ◽  
Milaid Stephan ◽  
Gesine Kögler
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Mononuclear Cells ◽  
Embryonic Stem ◽  
Human Tumor ◽  
Stem Cell Differentiation ◽  
Self Renewal ◽  
Oct4 Expression

Abstract The octamer-binding transcription factor 4 gene encodes a nuclear protein (Oct4, also known as Pou5F1 and Oct3/4) that belongs to a family of transcription factors containing the POU DNA-binding domain. Expression can be detected in embryonic stem cells as well as in adult stem cells, such as bone marrow-derived mesenchymal stem cells. Expression of Oct4 is downregulated coincident with stem cell differentiation and loss of expression leading to differentiation. A role for maintaining pluripotency and self-renewal of embryonic stem cells is ascribed to Oct4 as a pluripotency marker. Results describing Oct4 expression in differentiated cells, including peripheral blood mononuclear cells (PBMCs), neonatal and adult stem cells, as well as cancer cells, must be interpreted with caution. In several publications, Oct4 has been ascribed a function in maintaining self-renewal of adult stem cells. In contrast, other publications reported Oct4 expression in human tumor cells. Here, we summarize the recent findings on Oct4 expression and present possibilities and reasons why several false positive results on Oct4 expression still occur in the recent literature. Also, simple solutions are provided to avoid these positive signals.

scholarly journals Modulation of Differentiation of Embryonic Stem Cells by Polypyrrole: The Impact on Neurogenesis

2021 ◽  
Vol 22 (2) ◽  
pp. 501
Author(s):  
Kateřina Skopalová ◽  
Katarzyna Anna Radaszkiewicz ◽  
Věra Kašpárková ◽  
Jaroslav Stejskal ◽  
Patrycja Bober ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Active Role ◽  
Low Molecular Weight ◽  
Conducting Materials ◽  
The Impact ◽  
Erk Kinase

The active role of biomaterials in the regeneration of tissues and their ability to modulate the behavior of stem cells in terms of their differentiation is highly advantageous. Here, polypyrrole, as a representantive of electro-conducting materials, is found to modulate the behavior of embryonic stem cells. Concretely, the aqueous extracts of polypyrrole induce neurogenesis within embryonic bodies formed from embryonic stem cells. This finding ledto an effort to determine the physiological cascade which is responsible for this effect. The polypyrrole modulates signaling pathways of Akt and ERK kinase through their phosphorylation. These effects are related to the presence of low-molecular-weight compounds present in aqueous polypyrrole extracts, determined by mass spectroscopy. The results show that consequences related to the modulation of stem cell differentiation must also be taken into account when polypyrrole is considered as a biomaterial.

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