scholarly journals A quantitative comparison of human embryonic and induced stem cell proteomes

2021 ◽  
Author(s):  
Alejandro J. Brenes ◽  
Eva J. Griesser ◽  
Linda V Sinclair ◽  
Hao Jiang ◽  
Harunori Yoshikawa ◽  
...  

Human induced pluripotent stem cells (hiPSCs) have great potential to be used as alternatives to embryonic stem cells (hESCs) in regenerative medicine and disease modelling. However, a clear overview of their differences at the protein level is still incomplete. In this study we characterise the proteomes of hiPSC and hESC lines, where we find that they express a similar set of proteins but show consistent quantitative differences that can be masked by the normalisation methods. hiPSCs have a higher protein content, with over 1,500 proteins showing over two-fold increased expression. They also display proteomic differences in their mitochondria, with increased expression of mitochondrial transporters and metabolic proteins as well as mitochondrial translation machinery. The hiPSCs also show higher expression of important amino acid transporters, secreted proteins, and growth factors with potential to affect neighbouring cells, coupled with a systematic reduction in the expression levels of H1 histone variants. We conclude that despite hiPSCs and hESCs being highly similar cell types, they show important differences in protein expression that may be relevant for their use in clinical research.

Author(s):  
Anja Trillhaase ◽  
Marlon Maertens ◽  
Zouhair Aherrahrou ◽  
Jeanette Erdmann

AbstractStem cell technology has been around for almost 30 years and in that time has grown into an enormous field. The stem cell technique progressed from the first successful isolation of mammalian embryonic stem cells (ESCs) in the 1990s, to the production of human induced-pluripotent stem cells (iPSCs) in the early 2000s, to finally culminate in the differentiation of pluripotent cells into highly specialized cell types, such as neurons, endothelial cells (ECs), cardiomyocytes, fibroblasts, and lung and intestinal cells, in the last decades. In recent times, we have attained a new height in stem cell research whereby we can produce 3D organoids derived from stem cells that more accurately mimic the in vivo environment. This review summarizes the development of stem cell research in the context of vascular research ranging from differentiation techniques of ECs and smooth muscle cells (SMCs) to the generation of vascularized 3D organoids. Furthermore, the different techniques are critically reviewed, and future applications of current 3D models are reported. Graphical abstract


2020 ◽  
Vol 5 (1) ◽  
pp. 1-4 ◽  
Author(s):  
David Septian Sumanto Marpaung ◽  
Ayu Oshin Yap Sinaga

The four transcription factors OCT4, SOX2, KLF4 and c-MYC are highly expressed in embryonic stem cells (ESC) and their overexpression can induce pluripotency, the ability to differentiate into all cell types of an organism. The ectopic expression such transcription factors could reprogram somatic stem cells become induced pluripotency stem cells (iPSC), an embryonic stem cells-like. Production of recombinant pluripotency factors gain interests due to high demand from generation of induced pluripotent stem cells in regenerative medical therapy recently. This review will focus on demonstrate the recent advances in recombinant pluripotency factor production using various host.


2021 ◽  
Vol 26 ◽  
pp. 169-191
Author(s):  
Emma E. Redfield ◽  
Erin K. Luciano ◽  
Monica J. Sewell ◽  
Lucas A. Mitzel ◽  
Isaac J. Sanford ◽  
...  

This study looks at the number of clinical trials involving specific stem cell types. To our knowledge, this has never been done before. Stem cell clinical trials that were conducted at locations in the US and registered on the National Institutes of Health database at ‘clinicaltrials.gov’ were categorized according to the type of stem cell used (adult, cancer, embryonic, perinatal, or induced pluripotent) and the year that the trial was registered. From 1999 to 2014, there were 2,357 US stem cell clinical trials registered on ‘clinicaltrials.gov,’ and 89 percent were from adult stem cells and only 0.12 percent were from embryonic stem cells. This study concludes that embryonic stem cells should no longer be used for clinical study because of their irrelevance, moral questions, and induced pluripotent stem cells.


2020 ◽  
pp. 185-208
Author(s):  
John Parrington

Stem cells, which are ‘immortal’ cells that divide indefinitely and produce many different cell types, are central to how our body develops and maintains itself. Embryonic stem cells can give rise to all cell types in the body, and there has been lots of interest since their discovery in the 1980s in using such cells to generate new tissues or organs to replace diseased or faulty ones. More recently has come the discovery of induced pluripotent stem cells, which are normal skin cells taken from a person and genetically modified or tweaked chemically to give them stem cell properties. There is now hope that both of these types of stem cells might be used in ‘regenerative’ medicine, for instance in producing pancreatic cells that secrete insulin which could be used to treat diabetes. Perhaps the most remarkable breakthrough in recent years has been the discovery that stem cells introduced into a 3D matrix that is infused with chemicals that stimulate the development of particular cell types, can spontaneously form ‘organoids’, which have many of the cell types and even structural features of human organs such as hearts, kidneys, intestines, and even eyes and brains. Organoids make it possible to study how human organs develop but also this area of science raises many ethical issues. For instance, currently human brain organoids can only grow to the size of an embryonic brain, but if in the future they could be induced to grow to adult brain size, could they develop feelings and thoughts?


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.


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Catriona Kelly ◽  
Cara C. S. Flatt ◽  
Neville H. McClenaghan

The incidence of diabetes and the associated debilitating complications are increasing at an alarming rate worldwide. Current therapies for type 1 diabetes focus primarily on administration of exogenous insulin to help restore glucose homeostasis. However, such treatment rarely prevents the long-term complications of this serious metabolic disorder, including neuropathy, nephropathy, retinopathy, and cardiovascular disease. Whole pancreas or islet transplantations have enjoyed limited success in some individuals, but these approaches are hampered by the shortage of suitable donors and the burden of lifelong immunosuppression. Here, we review current approaches to differentiate nonislet cell types towards an islet-cell phenotype which may be used for larger-scale cell replacement strategies. In particular, the differentiation protocols used to direct embryonic stem cells, progenitor cells of both endocrine and nonendocrine origin, and induced pluripotent stem cells towards an islet-cell phenotype are discussed.


2010 ◽  
Vol 7 (suppl_6) ◽  
Author(s):  
Nigel G. Kooreman ◽  
Joseph C. Wu

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the ability (i) to duplicate indefinitely while maintaining pluripotency and (ii) to differentiate into cell types of all three embryonic germ layers. These two properties of ESCs and iPSCs make them potentially suitable for tissue engineering and cell replacement therapy for many different diseases, including Parkinson's disease, diabetes and heart disease. However, one critical obstacle in the clinical application of ESCs or iPSCs is the risk of teratoma formation. The emerging field of molecular imaging is allowing researchers to track transplanted ESCs or iPSCs in vivo , enabling early detection of teratomas.


Author(s):  
Moning Liu ◽  
Lixia Zhao ◽  
Zixin Wang ◽  
Hong Su ◽  
Tong Wang ◽  
...  

Pluripotent stem cells (PSCs) have the potential to differentiate to all cell types of an adult individual and are useful for studying mammalian development. Establishing induced pluripotent stem cells (iPSCs) capable of expressing pluripotent genes and differentiating to three germ layers will not only help to explain the mechanisms underlying somatic reprogramming but also lay the foundation for the establishment of sheep embryonic stem cells (ESCs) in vitro. In this study, sheep somatic cells were reprogrammed in vitro into sheep iPSCs with stable morphology, pluripotent marker expression, and differentiation ability, delivered by piggyBac transposon system with eight doxycycline (DOX)-inducible exogenous reprogramming factors: bovine OCT4, SOX2, KLF4, cMYC, porcine NANOG, human LIN28, SV40 large T antigen, and human TERT. Sheep iPSCs exhibited a chimeric contribution to the early blastocysts of sheep and mice and E6.5 mouse embryos in vitro. A transcriptome analysis revealed the pluripotent characteristics of somatic reprogramming and insights into sheep iPSCs. This study provides an ideal experimental material for further study of the construction of totipotent ESCs in sheep.


Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 703 ◽  
Author(s):  
Rafael Soares Lindoso ◽  
Tais H. Kasai-Brunswick ◽  
Gustavo Monnerat Cahli ◽  
Federica Collino ◽  
Adriana Bastos Carvalho ◽  
...  

Omics approaches have significantly impacted knowledge about molecular signaling pathways driving cell function. Induced pluripotent stem cells (iPSC) have revolutionized the field of biological sciences and proteomics and, in particular, has been instrumental in identifying key elements operating during the maintenance of the pluripotent state and the differentiation process to the diverse cell types that form organisms. This review covers the evolution of conceptual and methodological strategies in proteomics; briefly describes the generation of iPSC from a historical perspective, the state-of-the-art of iPSC-based proteomics; and compares data on the proteome and transcriptome of iPSC to that of embryonic stem cells (ESC). Finally, proteomics of healthy and diseased cells and organoids differentiated from iPSC are analyzed.


2020 ◽  
Vol 27 (21) ◽  
pp. 3448-3462
Author(s):  
Marco Piccoli ◽  
Andrea Ghiroldi ◽  
Michelle M. Monasky ◽  
Federica Cirillo ◽  
Giuseppe Ciconte ◽  
...  

The development of new therapeutic applications for adult and embryonic stem cells has dominated regenerative medicine and tissue engineering for several decades. However, since 2006, induced Pluripotent Stem Cells (iPSCs) have taken center stage in the field, as they promised to overcome several limitations of the other stem cell types. Nonetheless, other promising approaches for adult cell reprogramming have been attempted over the years, even before the generation of iPSCs. In particular, two years before the discovery of iPSCs, the possibility of synthesizing libraries of large organic compounds, as well as the development of high-throughput screenings to quickly test their biological activity, enabled the identification of a 2,6-disubstituted purine, named reversine, which was shown to be able to reprogram adult cells to a progenitor-like state. Since its discovery, the effect of reversine has been confirmed on different cell types, and several studies on its mechanism of action have revealed its central role in inhibitory activity on several kinases implicated in cell cycle regulation and cytokinesis. These key features, together with its chemical nature, suggested a possible use of the molecule as an anti-cancer drug. Remarkably, reversine exhibited potent cytotoxic activity against several tumor cell lines in vitro and a significant effect in decreasing tumor progression and metastatization in vivo. Thus, 15 years since its discovery, this review aims at critically summarizing the current knowledge to clarify the dual role of reversine as a dedifferentiating agent and anti-cancer drug.


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