scholarly journals MYCL promotes iPSC-like colony formation via MYC Box 0 and 2 domains

2021 ◽  
Author(s):  
Chiaki Akifuji ◽  
Mio Iwasaki ◽  
Yuka Kawahara ◽  
Chiho Sakurai ◽  
Yusheng Cheng ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Proteome Analysis ◽  
Cytoskeletal Proteins ◽  
The Body ◽  
Germline Transmission ◽  
Phenotypic Difference ◽  
Reprogramming Efficiency ◽  
Ipsc Generation ◽  
Low Efficiency ◽  
Induced Pluripotent

Abstract Induced pluripotent stem cells (iPSCs) have the potential to differentiate into any cell in the body and thus have attractive regenerative medicine potential. Current iPSC generation protocols, however, have low efficiency and show variable quality among clones. This variability influences the efficiency and reproducibility of iPSC differentiation. Our previous study reported that MYC proteins (c-MYC and MYCL) are important for the reprogramming efficiency and germline transmission of iPSCs, but that MYCL can generate iPSC colonies more efficiently than c-MYC. However, why c-MYC and MYCL cause different reprogramming efficiencies is unknown. In this study, we found that MYC Box 0 (MB0) and MB2, two functional domains conserved in the MYC protein family, contribute to the phenotypic difference and promote iPSC generation in MYCL-induced reprogramming. Proteome analysis suggested that in MYCL-induced reprogramming, cell adhesion-related cytoskeletal proteins are regulated by the MB0 domain, while RNA processes are regulated by the MB2 domain. These findings provide a molecular explanation for why MYCL has higher reprogramming efficiency than c-MYC.

scholarly journals MYCL promotes iPSC-like colony formation via MYC Box 0 and 2 domains

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chiaki Akifuji ◽  
Mio Iwasaki ◽  
Yuka Kawahara ◽  
Chiho Sakurai ◽  
Yu-Shen Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Pluripotent Stem Cells ◽  
Cytoskeletal Proteins ◽  
Germline Transmission ◽  
Phenotypic Differences ◽  
Reprogramming Efficiency ◽  
Cell Sources ◽  
Low Efficiency ◽  
Induced Pluripotent

AbstractHuman induced pluripotent stem cells (hiPSCs) can differentiate into cells of the three germ layers and are promising cell sources for regenerative medicine therapies. However, current protocols generate hiPSCs with low efficiency, and the generated iPSCs have variable differentiation capacity among different clones. Our previous study reported that MYC proteins (c-MYC and MYCL) are essential for reprogramming and germline transmission but that MYCL can generate hiPSC colonies more efficiently than c-MYC. The molecular underpinnings for the different reprogramming efficiencies between c-MYC and MYCL, however, are unknown. In this study, we found that MYC Box 0 (MB0) and MB2, two functional domains conserved in the MYC protein family, contribute to the phenotypic differences and promote hiPSC generation in MYCL-induced reprogramming. Proteome analyses suggested that in MYCL-induced reprogramming, cell adhesion-related cytoskeletal proteins are regulated by the MB0 domain, while the MB2 domain regulates RNA processes. These findings provide a molecular explanation for why MYCL has higher reprogramming efficiency than c-MYC.

scholarly journals Proteins Reprogramming: Present and Future

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Yang Yang ◽  
Bin Liu ◽  
Jianwen Dong ◽  
Liangming Zhang ◽  
Mao Pang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Chemical Compounds ◽  
Insertion Mutation ◽  
Potential Safety ◽  
Reprogramming Efficiency ◽  
Immunological Rejection ◽  
Clinical Interest ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) are of great clinical interest for they are derived from one’s own somatic cells and have the potential of committed differentiation without immunological rejection after autografting. However, the use of viral and other modified vectors may still cause tumorigenesis due to chromosome insertion mutation, leading to limited practical use. iPSCs generated by reprogramming proteins overcome the potential safety risk and complicated manipulation procedures, thus they own better application prospective, yet some technical difficulties need to be studied and resolved, for instance, low reprogramming efficiency, unclear transduction, and reprogramming mechanism. In this paper, we summarize the current progress of proteins reprogramming technology for generation of iPSCs and discuss the promising efficiency-improved reprogramming methods by proteins plus other kinds of chemical compounds.

scholarly journals Versatility of Induced Pluripotent Stem Cells (iPSCs) for Improving the Knowledge on Musculoskeletal Diseases

2020 ◽  
Vol 21 (17) ◽  
pp. 6124
Author(s):  
Clara Sanjurjo-Rodríguez ◽  
Rocío Castro-Viñuelas ◽  
María Piñeiro-Ramil ◽  
Silvia Rodríguez-Fernández ◽  
Isaac Fuentes-Boquete ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Musculoskeletal Diseases ◽  
The Body ◽  
Cellular Mechanisms ◽  
Induced Pluripotent ◽  
New Strategies

Induced pluripotent stem cells (iPSCs) represent an unlimited source of pluripotent cells capable of differentiating into any cell type of the body. Several studies have demonstrated the valuable use of iPSCs as a tool for studying the molecular and cellular mechanisms underlying disorders affecting bone, cartilage and muscle, as well as their potential for tissue repair. Musculoskeletal diseases are one of the major causes of disability worldwide and impose an important socio-economic burden. To date there is neither cure nor proven approach for effectively treating most of these conditions and therefore new strategies involving the use of cells have been increasingly investigated in the recent years. Nevertheless, some limitations related to the safety and differentiation protocols among others remain, which humpers the translational application of these strategies. Nonetheless, the potential is indisputable and iPSCs are likely to be a source of different types of cells useful in the musculoskeletal field, for either disease modeling or regenerative medicine. In this review, we aim to illustrate the great potential of iPSCs by summarizing and discussing the in vitro tissue regeneration preclinical studies that have been carried out in the musculoskeletal field by using iPSCs.

scholarly journals Pluripotent Stem Cells: Current Understanding and Future Directions

2016 ◽  
Vol 2016 ◽  
pp. 1-20 ◽  
Author(s):  
Antonio Romito ◽  
Gilda Cobellis
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
The Body ◽  
Human Embryos ◽  
Pluripotent Cell ◽  
Future Directions ◽  
The Family ◽  
Induced Pluripotent ◽  
Early Mouse ◽  
Distinct Features

Pluripotent stem cells have the ability to undergo self-renewal and to give rise to all cells of the tissues of the body. However, this definition has been recently complicated by the existence of distinct cellular states that display these features. Here, we provide a detailed overview of the family of pluripotent cell lines derived from early mouse and human embryos and compare them with induced pluripotent stem cells. Shared and distinct features of these cells are reported as additional hallmark of pluripotency, offering a comprehensive scenario of pluripotent stem cells.

Melatonin improves reprogramming efficiency and proliferation of bovine-induced pluripotent stem cells

2016 ◽  
Vol 61 (2) ◽  
pp. 154-167 ◽  
Author(s):  
Chunyu Bai ◽  
Xiangchen Li ◽  
Yuhua Gao ◽  
Ziao Yuan ◽  
Pengfei Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Reprogramming Efficiency ◽  
Induced Pluripotent

scholarly journals Biomedical Application of Dental Tissue-Derived Induced Pluripotent Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jung-Hwan Lee ◽  
Seog-Jin Seo
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Biomedical Application ◽  
Donor Site ◽  
Donor Site Morbidity ◽  
The Body ◽  
Dental Tissue ◽  
Induced Pluripotent

The academic researches and clinical applications in recent years found interest in induced pluripotent stem cells (iPSCs-) based regenerative medicine due to their pluripotency able to differentiate into any cell types in the body without using embryo. However, it is limited in generating iPSCs from adult somatic cells and use of these cells due to the low stem cell potency and donor site morbidity. In biomedical applications, particularly, dental tissue-derived iPSCs have been getting attention as a type of alternative sources for regenerating damaged tissues due to high potential of stem cell characteristics, easy accessibility and attainment, and their ectomesenchymal origin, which allow them to have potential for nerve, vessel, and dental tissue regeneration. This paper will cover the overview of dental tissue-derived iPSCs and their application with their advantages and drawbacks.

scholarly journals Technological Progress in Generation of Induced Pluripotent Stem Cells for Clinical Applications

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Seung-Ick Oh ◽  
Chang Kyu Lee ◽  
Kyung Jin Cho ◽  
Kyung-Ok Lee ◽  
Ssang-Goo Cho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Chromosomal Abnormalities ◽  
Patient Specific ◽  
Current State ◽  
Reprogramming Efficiency ◽  
Induced Pluripotent ◽  
Viral Dna Integration ◽  
Medical Interest

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is achieved by viral-mediated transduction of defined transcription factors. Generation of iPSCs is of great medical interest as they have the potential to be a source of patient-specific cells. For the eventual goal of clinical application, it is necessary to overcome the limitations of low reprogramming efficiency and chromosomal abnormalities due to viral DNA integration. In this paper, we summarize the current state of reprogramming technology for generation of iPSCs and also discuss potential approaches to the development of safe iPSCs for personalized cell-based replacement therapy.

scholarly journals Dot1L methyltransferase activity is a barrier to acquisition of pluripotency but not transdifferentiation

2019 ◽  
Author(s):  
Coral K. Wille ◽  
Rupa Sridharan
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Cell Types ◽  
Transcriptional Elongation ◽  
Mrna Levels ◽  
Mesenchymal To Epithelial Transition ◽  
Ipsc Generation ◽  
Induced Pluripotent

ABSTRACTThe ability of pluripotent stem cells to be poised to differentiate into any somatic cell type is partly derived from a unique chromatin structure that is depleted for transcriptional elongation associated epigenetic modifications, primarily H3K79 methylation. Inhibiting the H3K79 methyltransferase, Dot1L, increases the efficiency of reprogramming somatic cells to induced pluripotent stem cells (iPSCs) most potently at the mid-point of the process. Surprisingly, despite the enrichment of H3K79me2 on thousands of actively transcribed genes, Dot1L inhibition (Dot1Li) results in few changes in steady state mRNA levels during reprogramming. Dot1Li spuriously upregulates genes not involved in pluripotency and does not shutdown the somatic program. Depletion of the few genes that are downregulated, such as Nfix, enhances reprogramming efficiency in cooperation with Dot1Li. Contrary to the prevalent view, Dot1Li promotes iPSC generation beyond early phases of reprogramming such as the mesenchymal to epithelial transition and from already epithelial cell types including keratinocytes. Significantly, Dot1L inhibition does not enhance lineage conversion to neurons or muscle cells. Taken together, our results indicate that H3K79me is not a universal barrier of cell fate transitions but specifically protects somatic cells from reverting to the pluripotent state.

scholarly journals Transcription Factors Active in the Anterior Blastema of Schmidtea mediterranea

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1782
Author(s):  
Yoko Suzuki-Horiuchi ◽  
Henning Schmitz ◽  
Carlotta Barlassina ◽  
David Eccles ◽  
Martina Sinn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Pluripotent Stem Cells ◽  
The Body ◽  
Body Parts ◽  
Human Beings ◽  
Medical Treatments ◽  
Induced Pluripotent ◽  
Anterior Regeneration

Regeneration, the restoration of body parts after injury, is quite widespread in the animal kingdom. Species from virtually all Phyla possess regenerative abilities. Human beings, however, are poor regenerators. Yet, the progress of knowledge and technology in the fields of bioengineering, stem cells, and regenerative biology have fostered major advancements in regenerative medical treatments, which aim to regenerate tissues and organs and restore function. Human induced pluripotent stem cells can differentiate into any cell type of the body; however, the structural and cellular complexity of the human tissues, together with the inability of our adult body to control pluripotency, require a better mechanistic understanding. Planarians, with their capacity to regenerate lost body parts thanks to the presence of adult pluripotent stem cells could help providing such an understanding. In this paper, we used a top-down approach to shortlist blastema transcription factors (TFs) active during anterior regeneration. We found 44 TFs—31 of which are novel in planarian—that are expressed in the regenerating blastema. We analyzed the function of half of them and found that they play a role in the regeneration of anterior structures, like the anterior organizer, the positional instruction muscle cells, the brain, the photoreceptor, the intestine. Our findings revealed a glimpse of the complexity of the transcriptional network governing anterior regeneration in planarians, confirming that this animal model is the perfect playground to study in vivo how pluripotency copes with adulthood.

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