The Expression and Functional Roles of miRNAs in Embryonic and Lineage-Specific Stem Cells

The discovery of small non-coding RNAs began an interesting era in cellular and molecular biology. To date, miRNAs are the best recognized non-coding RNAs for maintenance and differentiation of pluripotent stem cells including embryonic stem cells (ES), induced pluripotent stem cells (iPSC), and cancer stem cells. ES cells are defined by their ability to self-renew, teratoma formation, and to produce numerous types of differentiated cells. Dual capacity of ES cells for self-renewal and differentiation is controlled by specific interaction with the neighboring cells and intrinsic signaling pathways from the level of transcription to translation. The ES cells have been the suitable model for evaluating the function of non-coding RNAs and in specific miRNAs. So far, the general function of the miRNAs in ES cells has been assessed in mammalian and non-mammalian stem cells. Nowadays, the evolution of sequencing technology led to the discovery of numerous miRNAs in human and mouse ES cells that their expression levels significantly changes during proliferation and differentiation. Several miRNAs have been identified in ectoderm, mesoderm, and endoderm cells, as well. This review would focus on recent knowledge about the expression and functional roles of miRNAs in embryonic and lineage-specific stem cells. It also describes that miRNAs might have essential roles in orchestrating the Waddington's landscape structure during development.

Download Full-text

Human embryonic stem cells

Journal of Cell Science ◽

10.1242/jcs.113.1.5 ◽

2000 ◽

Vol 113 (1) ◽

pp. 5-10 ◽

Cited By ~ 4

Author(s):

M.F. Pera ◽

B. Reubinoff ◽

A. Trounson

Keyword(s):

Stem Cells ◽

Cell Lines ◽

Embryonal Carcinoma ◽

Es Cells ◽

Embryonic Stem ◽

Early Embryo ◽

Carcinoma Cells ◽

Mouse Es Cells ◽

Undifferentiated State ◽

Human Es Cells

Embryonic stem (ES) cells are cells derived from the early embryo that can be propagated indefinitely in the primitive undifferentiated state while remaining pluripotent; they share these properties with embryonic germ (EG) cells. Candidate ES and EG cell lines from the human blastocyst and embryonic gonad can differentiate into multiple types of somatic cell. The phenotype of the blastocyst-derived cell lines is very similar to that of monkey ES cells and pluripotent human embryonal carcinoma cells, but differs from that of mouse ES cells or the human germ-cell-derived stem cells. Although our understanding of the control of growth and differentiation of human ES cells is quite limited, it is clear that the development of these cell lines will have a widespread impact on biomedical research.

Download Full-text

2. Embryonic stem cells

10.1093/actrade/9780198869290.003.0002 ◽

2021 ◽

pp. 21-37

Author(s):

Jonathan Slack

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Inner Cell Mass ◽

Es Cells ◽

Practical Importance ◽

Cell Mass ◽

Embryonic Stem ◽

Human Embryos ◽

Mouse Es Cells ◽

Stage Embryo

‘Embryonic stem cells’ focuses on embryonic stem (ES) cells, which are grown in tissue culture from the inner cell mass of a mammalian blastocyst-stage embryo. Human ES cells offer a potential route to making the kinds of cells needed for cell therapy. ES cells were originally prepared from mouse embryos. Although somewhat different, cells grown from inner cell masses of human embryos share many properties with mouse ES cells, such as being able to grow without limit and to generate differentiated cell types. Mouse ES cells have so far been of greater practical importance than those of humans because they have enabled a substantial research industry based on the creation of genetically modified mice.

Download Full-text

5. Tissue-specific stem cells

10.1093/actrade/9780198869290.003.0005 ◽

2021 ◽

pp. 75-89

Author(s):

Jonathan Slack

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Es Cells ◽

Embryonic Stem ◽

Molecular Characteristics ◽

Cell Surface Molecules ◽

Tissue Specific ◽

Surface Molecules ◽

Induced Pluripotent ◽

Tissue Specific Stem Cells

‘Tissue-specific stem cells’ explores tissue-specific stem cells, which are stem cells found in the postnatal body that are responsible for tissue renewal or for repair following damage. Tissue-specific stem cells share with pluripotent stem cells the same ability to persist indefinitely as a population, to reproduce themselves, and to generate differentiated progeny cells. However, tissue-specific stem cells share few molecular characteristics with embryonic stem (ES) cells or induced pluripotent stem cells (iPS cells), such as expression of specific transcription factors or cell surface molecules. Only renewal tissues have stem cells in the sense of a special population of cells that reproduce themselves and continue to generate differentiated progeny.

Download Full-text

Tyrosine kinase signalling in embryonic stem cells

Clinical Science ◽

10.1042/cs20070388 ◽

2008 ◽

Vol 115 (2) ◽

pp. 43-55 ◽

Cited By ~ 20

Author(s):

Cecilia Annerén

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Tyrosine Kinase ◽

Tyrosine Kinases ◽

Es Cells ◽

Embryonic Stem ◽

Cell Types ◽

Self Renewal ◽

Mouse Es Cells ◽

Wide Range

Pluripotent ES (embryonic stem) cells can be expanded in culture and induced to differentiate into a wide range of cell types. Self-renewal of ES cells involves proliferation with concomitant suppression of differentiation. Some critical and conserved pathways regulating self-renewal in both human and mouse ES cells have been identified, but there is also evidence suggesting significant species differences. Cytoplasmic and receptor tyrosine kinases play important roles in proliferation, survival, self-renewal and differentiation in stem, progenitor and adult cells. The present review focuses on the role of tyrosine kinase signalling for maintenance of the undifferentiated state, proliferation, survival and early differentiation of ES cells.

Download Full-text

Study of the C60 Fullerene on Differentiation of Mouse Embryonic Stem Cells

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.529-530.385 ◽

2012 ◽

Vol 529-530 ◽

pp. 385-390

Author(s):

Koichi Imai ◽

Fumio Watari ◽

Kazuaki Nakamura ◽

Akito Tanoue

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Experimental Method ◽

Es Cells ◽

Embryonic Stem ◽

Future Generations ◽

C60 Fullerene ◽

Biological Safety ◽

Mouse Es Cells

The risks of nanomaterials for future generations should be elucidated. Thus, it is important to establish an experimental method to accurately examine embryotoxicity. We have conducted anin vitroembryotoxicity test with mouse ES cells to examine the embryotoxicities of various nanomaterials. In this study, the C60 fullerene did not influence the differentiation of ES-D3 cells and "non embryotoxicity". In the future, the biological safety should be comprehensively examined by improving dispersion in medium.

Download Full-text

Hepatic differentiation of pluripotent stem cells

Biological Chemistry ◽

10.1515/bc.2009.120 ◽

2009 ◽

Vol 390 (10) ◽

Cited By ~ 15

Author(s):

Komal Loya ◽

Reto Eggenschwiler ◽

Kinarm Ko ◽

Malte Sgodda ◽

Francoise André ◽

...

Keyword(s):

Stem Cells ◽

Regenerative Medicine ◽

Pluripotent Stem Cells ◽

Ethical Issues ◽

Es Cells ◽

Embryonic Stem ◽

Hepatic Differentiation ◽

Alternative Source ◽

Organ Specific

Abstract In regenerative medicine pluripotent stem cells are considered to be a valuable self-renewing source for therapeutic cell transplantations, given that a functional organ-specific phenotype can be acquired by in vitro differentiation protocols. Furthermore, derivatives of pluripotent stem cells that mimic fetal progenitor stages could serve as an important tool to analyze organ development with in vitro approaches. Because of ethical issues regarding the generation of human embryonic stem (ES) cells, other sources for pluripotent stem cells are intensively studied. Like in less developed vertebrates, pluripotent stem cells can be generated from the female germline even in mammals, via parthenogenetic activation of oocytes. Recently, testis-derived pluripotent stem cells were derived from the male germline. Therefore, we compared two different hepatic differentiation approaches and analyzed the generation of definitive endoderm progenitor cells and their further maturation into a hepatic phenotype using murine parthenogenetic ES cells, germline-derived pluripotent stem cells, and ES cells. Applying quantitative RT-PCR, both germline-derived pluripotent cell lines show similar differentiation capabilities as normal murine ES cells and can be considered an alternative source for pluripotent stem cells in regenerative medicine.

Download Full-text

Differential regulation of lineage commitment in human and mouse primed pluripotent stem cells by NuRD

10.1101/2020.02.05.935544 ◽

2020 ◽

Author(s):

Ramy Ragheb ◽

Sarah Gharbi ◽

Julie Cramard ◽

Oluwaseun Ogundele ◽

Susan Kloet ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Pluripotent Stem Cells ◽

Es Cells ◽

Pluripotent Cells ◽

Down Regulation ◽

Mouse Es Cells ◽

The Right ◽

Human And Mouse ◽

Pluripotency Genes

AbstractDifferentiation of mammalian pluripotent cells involves large-scale changes in transcription and, among the molecules that orchestrate these changes, chromatin remodellers are essential to initiate, establish and maintain a new gene regulatory network. The NuRD complex is a highly conserved chromatin remodeller which fine-tunes gene expression in embryonic stem cells. While the function of NuRD in mouse pluripotent cells has been well defined, no study yet has defined NuRD function in human pluripotent cells. We investigated the structure and function of NuRD in human induced pluripotent stem cells (hiPSCs). Using immunoprecipitation followed by mass-spectrometry in hiPSCs and in naive or primed mouse pluripotent stem cells, we find that NuRD structure and biochemical interactors are generally conserved. Using RNA sequencing, we find that, whereas in mouse primed stem cells and in mouse naïve ES cells, NuRD is required for an appropriate level of transcriptional response to differentiation signals, hiPSCs require NuRD to initiate these responses. This difference indicates that mouse and human cells interpret and respond to induction of differentiation differently.Graphical AbstractNuRD acts like a conductor in an orchestra.A. In the presence of NuRD (pink blob figure, centre) differentiation occurs in an ordered fashion in both mouse (left) and human (right) ES cells. Gene expression changes in both cell types are tightly controlled with down-regulation of pluripotency genes and up-regulation of lineage appropriate genes. This is akin to a group of musicians producing musical notes in the right order and at the right amplitude to create a coherent piece of music. B. Loss of “the conductor” NuRD results in increased transcriptional noise in both systems, indicated here as a low-level blanket of sound in both systems. Consequences of MBD3/NuRD loss differs between human and mouse ES cells. In mouse ES cells, differentiation cues lead to some down-regulation of pluripotency genes and incomplete progression along a lineage appropriate pathway. This is like musicians who know that they should be making music but who lose their way without a conductor’s influence. In human iPS cells the background level of noise without NuRD results in a lack of order to gene expression changes in response to differentiation. The noise from these “musicians” would be truly awful.

Download Full-text

Human therapeutic cloning, pitfalls and lack luster because of rapid developments in induced pluripotent stem cell technology

Asian Biomedicine ◽

10.5372/1905-7415.0801.256 ◽

2014 ◽

Vol 8 (1) ◽

pp. 5-10

Author(s):

Song Hua ◽

Henry Chung ◽

Kuldip Sidhu

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Regenerative Medicine ◽

Somatic Cell ◽

Pluripotent Stem Cells ◽

Nuclear Transfer ◽

Es Cells ◽

Embryonic Stem ◽

Therapeutic Cloning ◽

Induced Pluripotent

AbstractBackground: Therapeutic cloning is the combination of somatic cell nuclear transfer (SCNT) and embryonic stem cell (ES) techniques to create specific ES cells that match those of a patient. Because ES cells derived by nuclear transfer (SCNT ES cells) are genetically identical to the donor, it will not generate rejection by the host’s immune system and thus therapeutically may be more acceptable. Induced pluripotent stem cells (iPS) are a type of pluripotent stem cell artificially derived from an adult somatic cell by inducing a forced expression of a set of specific pluripotent genes. In the past few years, rapid progress in reprogramming and iPS technology has been made, and it seems to shadow any progress made in SCNT programs.Objective: This review compares the application perspective of SCNT with that of iPS in regenerative medicine.Methods:We conducted a literature search using the MEDLINE (PubMed), Wiley InterScience, Springer, EBSCO, and Annual Reviews databases using the keywords “iPS”, “ES”, “SCNT” “induced pluripotent stem cells”, “embryonic stem cells”, “therapeutic cloning”, “regenerative medicine”, and “somatic cell nuclear transfer”. Only articles published in English were included in this review.Results: These two methods both have advantages and disadvantages. Nevertheless, by using SCNT to generate patient-specific cell lines, it eliminates complications by avoiding the use of viral vectors during iPS generation. Success in in vitro matured eggs from aged women and even differentiation of oocytes from germ stem cells will further enhance the application of SCNT in regenerative medicine.Conclusion: Human SCNT may be an appropriate mean of generating patient stem cell lines for clinical therapy in the near future.

Download Full-text

Suppression of TGF-β and ERK Signaling Pathways as a New Strategy to Provide Rodent and Non-Rodent Pluripotent Stem Cells

Current Stem Cell Research & Therapy ◽

10.2174/1871527318666190314110529 ◽

2019 ◽

Vol 14 (6) ◽

pp. 466-473 ◽

Cited By ~ 8

Author(s):

Maryam Farzaneh ◽

Zahra Derakhshan ◽

Jamal Hallajzadeh ◽

Neda Hosseini Sarani ◽

Armin Nejabatdoust ◽

...

Keyword(s):

Stem Cells ◽

Growth Factor ◽

Small Molecules ◽

Signaling Pathways ◽

Pluripotent Stem Cells ◽

Transforming Growth Factor ◽

Es Cells ◽

Embryonic Stem ◽

Erk Signaling ◽

New Strategy

Stem cells are unspecialized cells and excellent model in developmental biology and a promising approach to the treatment of disease and injury. In the last 30 years, pluripotent embryonic stem (ES) cells were established from murine and primate sources, and display indefinite replicative potential and the ability to differentiate to all three embryonic germ layers. Despite large efforts in many aspects of rodent and non-rodent pluripotent stem cell culture, a number of diverse challenges remain. Natural and synthetic small molecules (SMs) strategy has the potential to overcome these hurdles. Small molecules are typically fast and reversible that target specific signaling pathways, epigenetic processes and other cellular processes. Inhibition of the transforming growth factor-β (TGF-β/Smad) and fibroblast growth factor 4 (FGF4)/ERK signaling pathways by SB431542 and PD0325901 small molecules, respectively, known as R2i, enhances the efficiency of mouse, rat, and chicken pluripotent stem cells passaging from different genetic backgrounds. Therefore, the application of SM inhibitors of TGF-β and ERK1/2 with leukemia inhibitory factor (LIF) allows the cultivation of pluripotent stem cells in a chemically defined condition. In this review, we discuss recently emerging evidence that dual inhibition of TGF-β and FGF signaling pathways plays an important role in regulating pluripotency in both rodent and non-rodent pluripotent stem cells.

Download Full-text

Effects of Synthetic Neural Adhesion Molecule Mimetic Peptides and Related Proteins on the Cardiomyogenic Differentiation of Mouse Embryonic Stem Cells

Cellular Physiology and Biochemistry ◽

10.1159/000374044 ◽

2015 ◽

Vol 35 (6) ◽

pp. 2437-2450 ◽

Cited By ~ 2

Author(s):

Ruodan Xu ◽

Sureshkumar Perumal Srinivasan ◽

Poornima Sureshkumar ◽

Erastus Nembu Nembo ◽

Christoph Schäfer ◽

...

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Synthetic Peptides ◽

Es Cells ◽

Embryonic Stem ◽

Dependent Manner ◽

Es Cell ◽

Cardiomyogenic Differentiation ◽

Cellular Environment ◽

Structural And Functional Properties

Background/Aims: Pluripotent stem cells differentiating into cardiomyocyte-like cells in an appropriate cellular environment have attracted significant attention, given the potential use of such cells for regenerative medicine. However, the precise mechanisms of lineage specification of pluripotent stem cells are still largely to be explored. Identifying the role of various small synthetic peptides involved in cardiomyogenesis may provide new insights into pathways promoting cardiomyogenesis. Methods: In the present study, using a transgenic murine embryonic stem (ES) cell lineage expressing enhanced green fluorescent protein (EGFP) under the control of α-myosin heavy chain (α-MHC) promoter (pαMHC-EGFP), we investigated the cardiomyogenic effects of 7 synthetic peptides (Betrofin3, FGLs, FGLL, hNgf_C2, EnkaminE, Plannexin and C3) on cardiac differentiation. The expression of several cardiac-specific markers was determined by RT-PCR whereas the structural and functional properties of derived cardiomyocytes were examined by immunofluorescence and electrophysiology, respectively. Results: The results revealed that Betrofin3, an agonist of brain derived neurotrophic factor (BDNF) peptide exerted the most striking pro-cardiomyogenic effect on ES cells. We found that BDNF receptor, TrkB expression was up-regulated during differentiation. Treatment of differentiating cells with Betrofin3 between days 3 and 5 enhanced the expression of cardiac-specific markers and improved cardiomyocyte differentiation and functionality as revealed by genes regulation, flow cytometry and patch clamp analysis. Thus Betrofin3 may exert its cardiomyogenic effects on ES cells via TrkB receptor. Conclusion: Taken together, the results suggest that Betrofin3 modulates BDNF signaling with positive cardiomyogenic effect in stage and dose-dependent manner providing an effective strategy to increase ES cell-based generation of cardiomyocytes and offer a novel therapeutic approach to cardiac pathologies where BDNF levels are impaired.

Download Full-text