scholarly journals Cellular Reprogramming Using Defined Factors and MicroRNAs

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Takanori Eguchi ◽  
Takuo Kuboki

Development of human bodies, organs, and tissues contains numerous steps of cellular differentiation including an initial zygote, embryonic stem (ES) cells, three germ layers, and multiple expertized lineages of cells. Induced pluripotent stem (iPS) cells have been recently developed using defined reprogramming factors such as Nanog, Klf5, Oct3/4 (Pou5f1), Sox2, and Myc. This outstanding innovation is largely changing life science and medicine. Methods of direct reprogramming of cells into myocytes, neurons, chondrocytes, and osteoblasts have been further developed using modified combination of factors such as N-myc, L-myc, Sox9, and microRNAs in defined cell/tissue culture conditions. Mesenchymal stem cells (MSCs) and dental pulp stem cells (DPSCs) are also emerging multipotent stem cells with particular microRNA expression signatures. It was shown that miRNA-720 had a role in cellular reprogramming through targeting the pluripotency factor Nanog and induction of DNA methyltransferases (DNMTs). This review reports histories, topics, and idea of cellular reprogramming.

2021 ◽  
Vol 22 (9) ◽  
pp. 5011
Author(s):  
Daehwan Kim ◽  
Sangho Roh

Stem cell research is essential not only for the research and treatment of human diseases, but also for the genetic preservation and improvement of animals. Since embryonic stem cells (ESCs) were established in mice, substantial efforts have been made to establish true ESCs in many species. Although various culture conditions were used to establish ESCs in cattle, the capturing of true bovine ESCs (bESCs) has not been achieved. In this review, the difficulty of establishing bESCs with various culture conditions is described, and the characteristics of proprietary induced pluripotent stem cells and extended pluripotent stem cells are introduced. We conclude with a suggestion of a strategy for establishing true bESCs.


2021 ◽  
pp. 75-89
Author(s):  
Jonathan Slack

‘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.


2014 ◽  
Vol 8 (1) ◽  
pp. 5-10
Author(s):  
Song Hua ◽  
Henry Chung ◽  
Kuldip Sidhu

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.


2004 ◽  
Vol 24 (10) ◽  
pp. 4207-4220 ◽  
Author(s):  
Satoru Miyagi ◽  
Tetsuichiro Saito ◽  
Ken-ichi Mizutani ◽  
Norihisa Masuyama ◽  
Yukiko Gotoh ◽  
...  

ABSTRACT The Sox-2 gene is expressed in embryonic stem (ES) cells and neural stem cells. Two transcription enhancer regions, Sox-2 regulatory region 1 (SRR1) and SRR2, were described previously based on their activities in ES cells. Here, we demonstrate that these regulatory regions also exert their activities in neural stem cells. Moreover, our data reveal that, as in ES cells, both SRR1 and SRR2 show their activities rather specifically in multipotent neural stem or progenitor cells but cease to function in differentiated cells, such as postmitotic neurons. Systematic deletion and mutation analyses showed that the same or at least overlapping DNA elements of SRR2 are involved in its activity in both ES and neural stem or progenitor cells. Thus, SRR2 is the first example of an enhancer in which a single regulatory core sequence is involved in multipotent-state-specific expression in two different stem cells, i.e., ES and neural stem cells.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuanjie Ding ◽  
Yuanchun Yao ◽  
Xingmu Gong ◽  
Qi Zhuo ◽  
Jinhua Chen ◽  
...  

AbstractThe Jumonji domain-containing protein-3 (JMJD3) is a histone demethylase that regulates the trimethylation of histone H3 on lysine 27 (H3K27me3). H3K27me3 is an important epigenetic event associated with transcriptional silencing. JMJD3 has been studied extensively in immune diseases, cancer, and tumor development. There is a comprehensive epigenetic transformation during the transition of embryonic stem cells (ESCs) into specialized cells or the reprogramming of somatic cells to induced pluripotent stem cells (iPSCs). Recent studies have illustrated that JMJD3 plays a major role in cell fate determination of pluripotent and multipotent stem cells (MSCs). JMJD3 has been found to enhance self-renewal ability and reduce the differentiation capacity of ESCs and MSCs. In this review, we will focus on the recent advances of JMJD3 function in stem cell fate.


Reproduction ◽  
2014 ◽  
Vol 147 (6) ◽  
pp. R179-R188 ◽  
Author(s):  
Jingmei Hou ◽  
Shi Yang ◽  
Hao Yang ◽  
Yang Liu ◽  
Yun Liu ◽  
...  

Infertility is a major and largely incurable disease caused by disruption and loss of germ cells. It affects 10–15% of couples, and male factor accounts for half of the cases. To obtain human male germ cells ‘especially functional spermatids’ is essential for treating male infertility. Currently, much progress has been made on generating male germ cells, including spermatogonia, spermatocytes, and spermatids, from various types of stem cells. These germ cells can also be used in investigation of the pathology of male infertility. In this review, we focused on advances on obtaining male differentiated germ cells from different kinds of stem cells, with an emphasis on the embryonic stem (ES) cells, the induced pluripotent stem (iPS) cells, and spermatogonial stem cells (SSCs). We illustrated the generation of male differentiated germ cells from ES cells, iPS cells and SSCs, and we summarized the phenotype for these stem cells, spermatocytes and spermatids. Moreover, we address the differentiation potentials of ES cells, iPS cells and SSCs. We also highlight the advantages, disadvantages and concerns on derivation of the differentiated male germ cells from several types of stem cells. The ability of generating mature and functional male gametes from stem cells could enable us to understand the precise etiology of male infertility and offer an invaluable source of autologous male gametes for treating male infertility of azoospermia patients.


Author(s):  
Masaki Kinoshita ◽  
Michael Barber ◽  
William Mansfield ◽  
Yingzhi Cui ◽  
Daniel Spindlow ◽  
...  

SUMMARYPluripotent cells emerge via a naïve founder population in the blastocyst, acquire capacity for germline and soma formation, and then undergo lineage priming. Mouse embryonic stem (ES) cells and epiblast stem cells (EpiSCs) represent the initial naïve and final primed phases of pluripotency, respectively. Here we investigate the intermediate formative stage. Using minimal exposure to specification cues, we expand stem cells from formative mouse epiblast. Unlike ES cells or EpiSCs, formative stem (FS) cells respond directly to germ cell induction. They colonise chimaeras including the germline. Transcriptome analyses show retained pre-gastrulation epiblast identity. Gain of signal responsiveness and chromatin accessibility relative to ES cells reflect lineage capacitation. FS cells show distinct transcription factor dependencies from EpiSCs, relying critically on Otx2. Finally, FS cell culture conditions applied to human naïve cells or embryos support expansion of similar stem cells, consistent with a conserved attractor state on the trajectory of mammalian pluripotency.


2011 ◽  
Vol 23 (1) ◽  
pp. 248
Author(s):  
J. Y. Shin ◽  
Y. H. Jung ◽  
M. K. Gupta ◽  
S. J. Uhm ◽  
S. T. Shin ◽  
...  

Testis-derived male germ-line stem (GS) cells, the in vitro counterpart of spermatogonial stem cells, can acquire multipotency under appropriate culture conditions to become multipotent adult germ-line stem (maGS) cells, which, upon testicular transplantation, produce teratomas instead of initiating spermatogenesis. This study evaluated the DNA methylation and expression of imprinted microRNA (miRNA) in mouse GS and maGS cells. The GS and maGS cell lines were established essentially as described earlier (Jung et al. 2010 Mol. Hum. Reprod. PMID: 20610616) and were quantified for maternally (miR-296-3p, miR-296-5p, miR-483) and paternally (miR-127, miR-127-5p) imprinted miRNA by real-time TaqMan® MicroRNA assay and for DNA methylation at imprinting control regions of respective miRNA (Gnas-Nespas DMR, Igf2-H19 ICR, and Dlk1-Dio3 IG-DMR) by bisulfite genomic sequencing. Sperm and embryonic stem (ES) cells were used as controls for comparison. Results showed that, similar to sperm, expression of maternally imprinted miRNA was consistently higher (P < 0.001), whereas that of paternally imprinted miRNA was consistently lower (P < 0.001) in GS cells than in control ES cells. The DNA methylation analyses further confirmed that imprinted miRNA were androgenetic in GS cells. On the other hand, DNA methylation of maGS cells resembled that of ES cells, but the expression pattern of imprinted miRNA was intermediate between that of GS cells and ES cells. The expression of imprinted miRNA in GS and maGS cells was also altered during their in vitro differentiation but varied with both the differentiation stage and the miRNA. In conclusion, our data suggest that GS cells have androgenetic DNA methylation and expression of imprinted miRNA which changes to an ES cell-like pattern upon their conversion to maGS cells and, therefore, may serve as an epigenetic miRNA signature or molecular marker to distinguish GS cells from maGS cells. This work was supported by a grant (Code #200901FHT010305191) from BioGreen 21 Program, RDA, Republic of Korea.


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