The SOX Transcription Factors as Key Players in Pluripotent Stem Cells

2014 ◽  
Vol 23 (22) ◽  
pp. 2687-2699 ◽  
Author(s):  
Essam M. Abdelalim ◽  
Mohamed M. Emara ◽  
Prasanna R. Kolatkar
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Pluripotent Stem Cells ◽  
Key Players

Pluripotency transcription factors at the focus: the phase separation paradigm in stem cells

2021 ◽  
Author(s):  
Camila Oses ◽  
Martin Stortz ◽  
Paula Verneri ◽  
Alejandra Guberman ◽  
Valeria Levi
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Phase Separation ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
New Paradigm ◽  
Cell Fate Decisions ◽  
Key Players ◽  
New Ideas ◽  
Nuclear Processes

The transcription factors (TFs) OCT4, SOX2 and NANOG are key players of the gene regulatory network of pluripotent stem cells. Evidence accumulated in recent years shows that even small imbalances in the expression levels or relative concentrations of these TFs affect both, the maintenance of pluripotency and cell fate decisions. In addition, many components of the transcriptional machinery including RNA polymerases, cofactors and TFs such as those required for pluripotency, do not distribute homogeneously in the nucleus but concentrate in multiple foci influencing the delivery of these molecules to their DNA-targets. How cells control strict levels of available pluripotency TFs in this heterogeneous space and the biological role of these foci remain elusive. In recent years, a wealth of evidence led to propose that many of the nuclear compartments are formed through a liquid–liquid phase separation process. This new paradigm early penetrated the stem cells field since many key players of the pluripotency circuitry seem to phase-separate. Overall, the formation of liquid compartments may modulate the kinetics of biochemical reactions and consequently regulate many nuclear processes. Here, we review the state-of-the-art knowledge of compartmentalization in the cell nucleus and the relevance of this process for transcriptional regulation, particularly in pluripotent stem cells. We also highlight the recent advances and new ideas in the field showing how compartmentalization may affect pluripotency preservation and cell fate decisions.

scholarly journals Biological importance of OCT transcription factors in reprogramming and development

2021 ◽  
Author(s):  
Kee-Pyo Kim ◽  
Dong Wook Han ◽  
Johnny Kim ◽  
Hans R. Schöler
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ectopic Expression ◽  
Donor Cell ◽  
Structural Components ◽  
Oct4 Expression ◽  
Reprogramming Factors ◽  
Induced Pluripotent

AbstractEctopic expression of Oct4, Sox2, Klf4 and c-Myc can reprogram somatic cells into induced pluripotent stem cells (iPSCs). Attempts to identify genes or chemicals that can functionally replace each of these four reprogramming factors have revealed that exogenous Oct4 is not necessary for reprogramming under certain conditions or in the presence of alternative factors that can regulate endogenous Oct4 expression. For example, polycistronic expression of Sox2, Klf4 and c-Myc can elicit reprogramming by activating endogenous Oct4 expression indirectly. Experiments in which the reprogramming competence of all other Oct family members tested and also in different species have led to the decisive conclusion that Oct proteins display different reprogramming competences and species-dependent reprogramming activity despite their profound sequence conservation. We discuss the roles of the structural components of Oct proteins in reprogramming and how donor cell epigenomes endow Oct proteins with different reprogramming competences.

scholarly journals A mini review on production of pluripotency factors (Oct4, Sox2, Klf4 and c-Myc) through recombinant protein technology

2020 ◽  
Vol 5 (1) ◽  
pp. 1-4 ◽  
Author(s):  
David Septian Sumanto Marpaung ◽  
Ayu Oshin Yap Sinaga
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Pluripotent Stem Cells ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Cell Types ◽  
Induced Pluripotency ◽  
Pluripotency Factors ◽  
Induced Pluripotent

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.

Analysis of the transcription factors and their regulatory roles during a step-by-step differentiation of induced pluripotent stem cells into hepatocyte-like cells

2019 ◽  
Vol 15 (6) ◽  
pp. 383-398 ◽  
Author(s):  
Yannick Tauran ◽  
Stéphane Poulain ◽  
Myriam Lereau-Bernier ◽  
Mathieu Danoy ◽  
Marie Shinohara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Induced Pluripotent Stem Cells ◽  
Transcriptome Analysis ◽  
Pluripotent Stem Cells ◽  
Original Method ◽  
Induced Pluripotent

Human induced pluripotent stem cells have been investigated through a sequential in vitro step-by-step differentiation into hepatocyte-like cells using nanoCAGE, an original method for promoters, transcription factors, and transcriptome analysis.

Generation of Induced Pluripotent Stem Cells From Primary Chronic Myelogenous Leukemia Patient Sample.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1206-1206
Author(s):  
Keiki Kumano ◽  
Shunya Arai ◽  
Koki Ueda ◽  
Kumi Nakazaki ◽  
Yasuhiko Kamikubo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Induced Pluripotent Stem Cells ◽  
Chronic Myelogenous Leukemia ◽  
Pluripotent Stem Cells ◽  
Hematological Malignancies ◽  
Hematological Malignancy ◽  
Myelogenous Leukemia ◽  
Hematopoietic Progenitors ◽  
Induced Pluripotent

Abstract Abstract 1206 Introduction: Induced pluripotent stem cells (iPSCs) can be generated from various cell types by the expression of defined transcription factors. In addition to the regenerative medicine, iPSCs have been used for the study of the pathogenesis of inherited genetic disease. Recently, it was reported that iPSCs were generated not only from normal tissue, but also from malignant cells. In those cases, cancer cells themselves must be the starting material from which iPSCs are derived. However, in almost all the cases, they used the established cell lines (chronic myelogenous leukemia (CML), gastrointestinal cancers, and melanoma) except for the JAK2-V617F mutation (+) polycythemia vera (PV) patient. In this study, we established the iPSCs from primary CML patient sample. Results: After obtaining informed consent, bone marrow cells from CML patient were reprogrammed by introducing the transcription factors Oct3/4, Sox2, KLF4, and c-myc. To improve the efficiency of the development of iPSCs, we added valproic acid (VPA), a histone deacetylase inhibitor, to the culture. Two CML derived iPSCs (CML-iPSCs) were generated. CML-iPSCs expressed the pluripotency markers such as SSEA-4 and Tra-1-60, and the endogenous expression of embryonic stem cell (ESC) characteristic transcripts (Oct3/4, Sox2, KLF4, Nanog, LIN28, REX1) was confirmed by RT-PCR. Oct4 and Nanog promoter regions were demetylated in the CML-iPSCs. Although CML-iPSCs expressed bcr-abl, they were resistant to the imatinib. Then we differentiated them into hematopoietic progenitors within the ‘unique sac-like structures’ (iPS-sacs). This method was reported to be able to produce the hematopoietic progenitors with higher efficiency than the usual embryoid body formation method using human ESCs (Takayama et al., Blood, 111, 5298–306, 2008). The hematopoietic progenitors showed the hematopoietic marker CD45 and immature marker CD34, and recovered the sensitivity to the imatinib, which recapitulated the feature of initial CML disease. Then we investigated the mechanism of the resistance to the imatinib in CML-iPSCs. The phosphorylation state of ERK1/2, AKT, and STAT5, which are the essential for the survival of bcr-abl (+) hematopoietic progenitors, were evaluated after imatinib treatment in CML-iPSCs. The phosphorylation of ERK1/2 and AKT, which were also essential for the maintenance of iPSCs, were unchanged after treatment, although STAT5 was not activated both before and after treatment. These results showed that the signaling for iPSCs maintenance compensated for the inhibition of bcr-abl in CML-iPSCs and that the oncogene addiction was lost in CML-iPSCs. Conclusion: We generated the iPSCs from primary CML patient samples, re-differentiated them into hematopoietic lineage and showed the recapitulation of the features of initial disease. Primary samples of hematological malignancy are usually difficult to be expanded. However, if once they are reprogrammed to iPSCs, they can expand unlimitedly. As a result, we can obtain the genetically abnormal hematopoietic cells continuously by re-differentiating them into hematopoietic cells and use them for the studies which require the large number of living cells such as the analysis for leukemia stem cells or drug screening. Thus iPSCs technology would be useful for the study of hematological malignancy, especially for which animal model was not established such as myelodysplastic syndrome and be applicable for other cancers than hematological malignancies. We are now trying to establish the iPSCs derived from other hematological malignancies. Disclosures: No relevant conflicts of interest to declare.

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