scholarly journals Liver Development, Regeneration, and Carcinogenesis

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.

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.


2013 ◽  
Vol 91 (12) ◽  
pp. 985-998 ◽  
Author(s):  
Sreejit Parameswaran ◽  
Sujeet Kumar ◽  
Rama Shanker Verma ◽  
Rajendra K. Sharma

The success of any work with isolated cardiomyocytes depends on the reproducibility of cell isolation, because the cells do not divide. To date, there is no suitable in vitro model to study human adult cardiac cell biology. Although embryonic stem cells and induced pluripotent stem cells are able to differentiate into cardiomyocytes in vitro, the efficiency of this process is low. Isolation and expansion of human cardiomyocyte progenitor cells from cardiac surgical waste or, alternatively, from fetal heart tissue is another option. However, to overcome various issues related to human tissue usage, especially ethical concerns, researchers use large- and small-animal models to study cardiac pathophysiology. A simple model to study the changes at the cellular level is cultures of cardiomyocytes. Although primary murine cardiomyocyte cultures have their own advantages and drawbacks, alternative strategies have been developed in the last two decades to minimise animal usage and interspecies differences. This review discusses the use of freshly isolated murine cardiomyocytes and cardiomyocyte alternatives for use in cardiac disease models and other related studies.


2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Ivana Acimovic ◽  
Aleksandra Vilotic ◽  
Martin Pesl ◽  
Alain Lacampagne ◽  
Petr Dvorak ◽  
...  

Human pluripotent stem cells (hPSCs), namely, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), with their ability of indefinite self-renewal and capability to differentiate into cell types derivatives of all three germ layers, represent a powerful research tool in developmental biology, for drug screening, disease modelling, and potentially cell replacement therapy. Efficient differentiation protocols that would result in the cell type of our interest are needed for maximal exploitation of these cells. In the present work, we aim at focusing on the protocols for differentiation of hPSCs into functional cardiomyocytesin vitroas well as achievements in the heart disease modelling and drug testing on the patient-specific iPSC-derived cardiomyocytes (iPSC-CMs).


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Shanshan Hu ◽  
Ge Shan

Noncoding RNAs are critical regulatory factors in essentially all forms of life. Stem cells occupy a special position in cell biology and Biomedicine, and emerging results show that multiple ncRNAs play essential roles in stem cells. We discuss some of the known ncRNAs in stem cells such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, adult stem cells, and cancer stem cells with a focus on long ncRNAs. Roles and functional mechanisms of these lncRNAs are summarized, and insights into current and future studies are presented.


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.


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.


Genetika ◽  
2021 ◽  
Vol 53 (2) ◽  
pp. 813-823
Author(s):  
Sanja Rascanin ◽  
Mirjana Jovanovic ◽  
Dejan Stevanovic ◽  
Nemanja Rancic

The discovery of Induced Pluripotent Stem Cells (iPSCs) opened the possibilities for reprogramming adult somatic cells back to a pluripotent state in vitro by inducing a forced expression of specific transcription factors. Thus, iPSCs might have potential application in regenerative medicine, transplantation, avoidance of tissue rejection, disease modeling, and drug testing. Because of apparent ethical issues connected with donation and derivation of biomaterials, iPSCs are considered as a research alternative to ethically highly disputed Embryonic Stem Cells (ESCs). Objective: The aim of this paper was to describe the development of a questionnaire for evaluating information, knowledge, and attitudes on donation, storage, and application of iPSCs (i.e., the QIPSC). We performed a prospective qualitative study based on the development, validation and reliability testing of the QIPSC. The study included 122 respondents and the final version of the QIPSC with 34 items. The reliability analysis for part of information and knowledge of respondents according to iPSCs was then performed with the questions included in this two-component model and obtained a Cronbach's alpha value of 0.783 and 0.870, respectively. It has been shown that the range of correct answers to questions in part of knowledge of respondents according to iPSCs was from 17.2-63.1%. The results of our study show that the QIPSC was a unique, reliable, and valid questionnaire for assessing the level of information, knowledge, and attitudes on donation, storage, and application of iPSCs.


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