scholarly journals PRMT7: A Pivotal Arginine Methyltransferase in Stem Cells and Development

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Bingyuan Wang ◽  
Mingrui Zhang ◽  
Zhiguo Liu ◽  
Yulian Mu ◽  
Kui Li

Protein arginine methylation is a posttranslational modification catalyzed by protein arginine methyltransferases (PRMTs), which play critical roles in many biological processes. To date, nine PRMT family members, namely, PRMT1, 2, 3, 4, 5, 6, 7, 8, and 9, have been identified in mammals. Among them, PRMT7 is a type III PRMT that can only catalyze the formation of monomethylarginine and plays pivotal roles in several kinds of stem cells. It has been reported that PRMT7 is closely associated with embryonic stem cells, induced pluripotent stem cells, muscle stem cells, and human cancer stem cells. PRMT7 deficiency or mutation led to severe developmental delay in mice and humans, which is possibly due to its crucial functions in stem cells. Here, we surveyed and summarized the studies on PRMT7 in stem cells and development in mice and humans and herein provide a discussion of the underlying molecular mechanisms. Furthermore, we also discuss the roles of PRMT7 in cancer, adipogenesis, male reproduction, cellular stress, and cellular senescence, as well as the future perspectives of PRMT7-related studies. Overall, PRMT7 mediates the proliferation and differentiation of stem cells. Deficiency or mutation of PRMT7 causes developmental delay, including defects in skeletal muscle, bone, adipose tissues, neuron, and male reproduction. A better understanding of the roles of PRMT7 in stem cells and development as well as the underlying mechanisms will provide information for the development of strategies for in-depth research of PRMT7 and stem cells as well as their applications in life sciences and medicine.

Author(s):  
Lulu Ji ◽  
Lin Wang

Human placenta is vital for fetal development, and act as an interface between the fetus and the expecting mother. Abnormal placentati on underpins various pregnancy complications such as miscarriage, pre-eclampsia and intrauterine growth restriction. Despite the important role of placenta, the molecular mechanisms governing placental formation and trophoblast cell lineage specification is poorly understand. It is mostly due to the lack of appropriate model system. The great various in placental types across mammals make it limit for the use of laboratory animals in studying human placental development. However, over the past few years, alternative methods have been employed, including human embryonic stem cells, induced pluripotent stem cells, human trophoblast stem cell, and 3-dimensional organoids. Herein, we summarize the present knowledge about human development, differentiated cell types in the trophoblast epithelium and current human placental trophoblast model systems.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Junhao Deng ◽  
Yiling Zhang ◽  
Yong Xie ◽  
Licheng Zhang ◽  
Peifu Tang

Spinal cord injury (SCI) is an intractable and worldwide difficult medical challenge with limited treatments. Neural stem/progenitor cell (NS/PC) transplantation derived from fetal tissues or embryonic stem cells (ESCs) has demonstrated therapeutic effects via replacement of lost neurons and severed axons and creation of permissive microenvironment to promote repair of spinal cord and axon regeneration but causes ethnical concerns and immunological rejections as well. Thus, the implementation of induced pluripotent stem cells (iPSCs), which can be generated from adult somatic cells and differentiated into NS/PCs, provides an effective alternation in the treatment of SCI. However, as researches further deepen, there is accumulating evidence that the use of iPSC-derived NS/PCs shows mounting concerns of safety, especially the tumorigenicity. This review discusses the tumorigenicity of iPSC-derived NS/PCs focusing on the two different routes of tumorigenicity (teratomas and true tumors) and underlying mechanisms behind them, as well as possible solutions to circumvent them.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandro Rosa ◽  
Monica Ballarino

Pluripotent stem cells (PSCs) represent a unique kind of stem cell, as they are able to indefinitely self-renew and hold the potential to differentiate into any derivative of the three germ layers. As such, human Embryonic Stem Cells (hESCs) and human induced Pluripotent Stem Cells (hiPSCs) provide a unique opportunity for studying the earliest steps of human embryogenesis and, at the same time, are of great therapeutic interest. The molecular mechanisms underlying pluripotency represent a major field of research. Recent evidence suggests that a complex network of transcription factors, chromatin regulators, and noncoding RNAs exist in pluripotent cells to regulate the balance between self-renewal and multilineage differentiation. Regulatory noncoding RNAs come in two flavors: short and long. The first class includes microRNAs (miRNAs), which are involved in the posttranscriptional regulation of cell cycle and differentiation in PSCs. Instead, long noncoding RNAs (lncRNAs) represent a heterogeneous group of long transcripts that regulate gene expression at transcriptional and posttranscriptional levels. In this review, we focus on the role played by lncRNAs in the maintenance of pluripotency, emphasizing the interplay between lncRNAs and other pivotal regulators in PSCs.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Giuseppe Maria de Peppo ◽  
Darja Marolt

Stem cells divide by asymmetric division and display different degrees of potency, or ability to differentiate into various specialized cell types. Owing to their unique regenerative capacity, stem cells have generated great enthusiasm worldwide and represent an invaluable tool with unprecedented potential for biomedical research and therapeutic applications. Stem cells play a central role in the understanding of molecular mechanisms regulating tissue development and regeneration in normal and pathological conditions and open large possibilities for the discovery of innovative pharmaceuticals to treat the most devastating diseases of our time. Not least, their intrinsic characteristics allow the engineering of functional tissues for replacement therapies that promise to revolutionize the medical practice in the near future. In this paper, the authors present the characteristics of pluripotent stem cells and new developments of transdifferentiation technologies and explore some of the biomedical applications that this emerging technology is expected to empower.


Reproduction ◽  
2013 ◽  
Vol 146 (6) ◽  
pp. 569-579 ◽  
Author(s):  
Anran Fan ◽  
Kuiying Ma ◽  
Xinglan An ◽  
Yu Ding ◽  
Peipei An ◽  
...  

TET1 is implicated in maintaining the pluripotency of embryonic stem cells. However, its precise effects on induced pluripotent stem cells (iPSCs), and particularly on porcine iPSCs (piPSCs), are not well defined. To investigate the role of TET1 in the pluripotency and differentiation of piPSCs, piPSCs were induced from porcine embryonic fibroblasts by overexpression ofPOU5F1(OCT4),SOX2,KLF4, andMYC(C-MYC). siRNAs targeting toTET1were used to transiently knockdown the expression ofTET1in piPSCs. Morphological abnormalities and loss of the undifferentiated state of piPSCs were observed in the piPSCs after the downregulation ofTET1. The effects ofTET1knockdown on the expression of key stem cell factors and differentiation markers were analyzed to gain insights into the molecular mechanisms underlying the phenomenon. The results revealed that knockdown ofTET1resulted in the downregulated expression of pluripotency-related genes, such asLEFTY2,KLF2, andSOX2, and the upregulated expression of differentiation-related genes includingPITX2,HAND1,GATA6, andLEF1. However,POU5F1,MYC,KLF4, andNANOGwere actually not downregulated. Further analysis showed that the methylation levels of the promoters forPOU5F1andMYCincreased significantly afterTET1downregulation, whereas there were no obvious changes in the promoters ofSOX2,KLF4, andNANOG. The methylation of the whole genome increased, while hydroxymethylation slightly declined. Taken together, these results suggest thatTET1may play important roles in the self-renewal of piPSCs and the maintenance of their characteristics by regulating the expression of genes and the DNA methylation.


2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Janet W. C. Kung ◽  
Ian S. Currie ◽  
Stuart J. Forbes ◽  
James A. Ross

The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1470
Author(s):  
Giuseppe Scesa ◽  
Raffaella Adami ◽  
Daniele Bottai

The production of induced pluripotent stem cells (iPSCs) represent a breakthrough in regenerative medicine, providing new opportunities for understanding basic molecular mechanisms of human development and molecular aspects of degenerative diseases. In contrast to human embryonic stem cells (ESCs), iPSCs do not raise any ethical concerns regarding the onset of human personhood. Still, they present some technical issues related to immune rejection after transplantation and potential tumorigenicity, indicating that more steps forward must be completed to use iPSCs as a viable tool for in vivo tissue regeneration. On the other hand, cell source origin may be pivotal to iPSC generation since residual epigenetic memory could influence the iPSC phenotype and transplantation outcome. In this paper, we first review the impact of reprogramming methods and the choice of the tissue of origin on the epigenetic memory of the iPSCs or their differentiated cells. Next, we describe the importance of induction methods to determine the reprogramming efficiency and avoid integration in the host genome that could alter gene expression. Finally, we compare the significance of the tissue of origin and the inter-individual genetic variation modification that has been lightly evaluated so far, but which significantly impacts reprogramming.


Acta Naturae ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 39-47 ◽  
Author(s):  
А. V. Selenina ◽  
А. S. Tsimokha ◽  
А. N. Tomilin

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are subjects of high interest not only in basic research, but also in various applied fields, particularly, in regenerative medicine. Despite the tremendous interest to these cells, the molecular mechanisms that control protein homeostasis in these cells remain largely unknown. The ubiquitin-proteasome system (UPS) acts via post-translational protein modifications and protein degradation and, therefore, is involved in the control of virtually all cellular processes: cell cycle, self-renewal, signal transduction, transcription, translation, oxidative stress, immune response, apoptosis, etc. Therefore, studying the biological role and action mechanisms of the UPS in pluripotent cells will help to better understand the biology of cells, as well as to develop novel approaches for regenerative medicine.


Author(s):  
Abdullah El-Sayes

The isolation of human embryonic stem cells in 1998 has since fueled the ideology that stem cells may eventually be used for human disease therapies as well as the regeneration of tissues and organs. The transformation of somatic cells to a pluripotent state via somatic nuclear transfer and embryonic stem cell fusion brought the scientific community nearer to understanding the molecular mechanisms that govern cellular pluripotency. In 2006, the first induced pluripotent stem (iPS) cell was reported, where a mouse somatic cell was successfully converted to a pluripotent state via transduction of four essential factors. This cellular breakthrough has allowed for robust scientific investigations of human diseases that were once extremely difficult to study. Scientists and pharmaceuticals now use iPS cells as means for disease investigations, drug development and cell or tissue transplantation. There is little doubt that scientific progress on iPS cells will change many aspects of medicine in the next couple of decades.


2021 ◽  
Vol 22 (5) ◽  
pp. 2619
Author(s):  
Sunhee Jang ◽  
Kijun Lee ◽  
Ji Hyeon Ju

Osteoarthritis (OA) is a degenerative and chronic joint disease characterized by clinical symptoms and distortion of joint tissues. It primarily damages joint cartilage, causing pain, swelling, and stiffness around the joint. It is the major cause of disability and pain. The prevalence of OA is expected to increase gradually with the aging population and increasing prevalence of obesity. Many potential therapeutic advances have been made in recent years due to the improved understanding of the underlying mechanisms, diagnosis, and management of OA. Embryonic stem cells and induced pluripotent stem cells differentiate into chondrocytes or mesenchymal stem cells (MSCs) and can be used as a source of injectable treatments in the OA joint cavity. MSCs are known to be the most studied cell therapy products in cell-based OA therapy owing to their ability to differentiate into chondrocytes and their immunomodulatory properties. They have the potential to improve cartilage recovery and ultimately restore healthy joints. However, despite currently available therapies and advances in research, unfulfilled medical needs persist for OA treatment. In this review, we focused on the contents of non-cellular and cellular therapies for OA, and briefly summarized the results of clinical trials for cell-based OA therapy to lay a solid application basis for clinical research.


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