scholarly journals Cell stemness is maintained upon concurrent expression of RB and the mitochondrial ribosomal protein S18-2

2020 ◽  
Vol 117 (27) ◽  
pp. 15673-15683
Author(s):  
Muhammad Mushtaq ◽  
Larysa Kovalevska ◽  
Suhas Darekar ◽  
Alexandra Abramsson ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ribosomal Protein ◽  
Severe Combined Immunodeficiency ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Ring Finger ◽  
Histone H2a ◽  
Mitochondrial Ribosomal Protein ◽  
Primary Mouse

Stemness encompasses the capability of a cell for self-renewal and differentiation. The stem cell maintains a balance between proliferation, quiescence, and regeneration via interactions with the microenvironment. Previously, we showed that ectopic expression of the mitochondrial ribosomal protein S18-2 (MRPS18-2) led to immortalization of primary fibroblasts, accompanied by induction of an embryonic stem cell (ESC) phenotype. Moreover, we demonstrated interaction between S18-2 and the retinoblastoma-associated protein (RB) and hypothesized that the simultaneous expression of RB and S18-2 is essential for maintaining cell stemness. Here, we experimentally investigated the role of S18-2 in cell stemness and differentiation. Concurrent expression of RB and S18-2 resulted in immortalization ofRb1−/−primary mouse embryonic fibroblasts and in aggressive tumor growth in severe combined immunodeficiency mice. These cells, which express both RB and S18-2 at high levels, exhibited the potential to differentiate into various lineages in vitro, including osteogenic, chondrogenic, and adipogenic lineages. Mechanistically, S18-2 formed a multimeric protein complex with prohibitin and the ring finger protein 2 (RNF2). This molecular complex increased the monoubiquitination of histone H2ALys119, a characteristic trait of ESCs, by enhanced E3-ligase activity of RNF2. Furthermore, we found enrichment of KLF4 at theS18-2promoter region and that theS18-2expression is positively correlated withKLF4levels. Importantly, knockdown of S18-2 in zebrafish larvae led to embryonic lethality. Collectively, our findings suggest an important role for S18-2 in cell stemness and differentiation and potentially also in cancerogenesis.

scholarly journals The TGFβ Family in Human Placental Development at the Fetal-Maternal Interface

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 453
Author(s):  
Susana M. Chuva de Sousa Lopes ◽  
Marta S. Alexdottir ◽  
Gudrun Valdimarsdottir
Keyword(s):  
Stem Cell ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Cell Model ◽  
Embryonic Stem ◽  
Model Systems ◽  
Special Focus ◽  
Placental Development

Emerging data suggest that a trophoblast stem cell (TSC) population exists in the early human placenta. However, in vitro stem cell culture models are still in development and it remains under debate how well they reflect primary trophoblast (TB) cells. The absence of robust protocols to generate TSCs from humans has resulted in limited knowledge of the molecular mechanisms that regulate human placental development and TB lineage specification when compared to other human embryonic stem cells (hESCs). As placentation in mouse and human differ considerably, it is only with the development of human-based disease models using TSCs that we will be able to understand the various diseases caused by abnormal placentation in humans, such as preeclampsia. In this review, we summarize the knowledge on normal human placental development, the placental disease preeclampsia, and current stem cell model systems used to mimic TB differentiation. A special focus is given to the transforming growth factor-beta (TGFβ) family as it has been shown that the TGFβ family has an important role in human placental development and disease.

scholarly journals The dyskerin ribonucleoprotein complex as an OCT4/SOX2 coactivator in embryonic stem cells

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Yick W Fong ◽  
Jaclyn J Ho ◽  
Carla Inouye ◽  
Robert Tjian
Keyword(s):  
Stem Cell ◽  
Es Cells ◽  
Embryonic Stem ◽  
In Vitro Transcription ◽  
Specific Gene ◽  
Transcriptional Level ◽  
Ips Cell ◽  
Ribonucleoprotein Complex ◽  
Transcription System

Acquisition of pluripotency is driven largely at the transcriptional level by activators OCT4, SOX2, and NANOG that must in turn cooperate with diverse coactivators to execute stem cell-specific gene expression programs. Using a biochemically defined in vitro transcription system that mediates OCT4/SOX2 and coactivator-dependent transcription of the Nanog gene, we report the purification and identification of the dyskerin (DKC1) ribonucleoprotein complex as an OCT4/SOX2 coactivator whose activity appears to be modulated by a subset of associated small nucleolar RNAs (snoRNAs). The DKC1 complex occupies enhancers and regulates the expression of key pluripotency genes critical for self-renewal in embryonic stem (ES) cells. Depletion of DKC1 in fibroblasts significantly decreased the efficiency of induced pluripotent stem (iPS) cell generation. This study thus reveals an unanticipated transcriptional role of the DKC1 complex in stem cell maintenance and somatic cell reprogramming.

Derivation of goat embryonic stem cell-like cell lines from in vitro produced parthenogenetic blastocysts

2013 ◽  
Vol 113 (1) ◽  
pp. 145-153 ◽  
Author(s):  
Arun Kumar De ◽  
Shweta Garg ◽  
Dinesh Kumar Singhal ◽  
Hrudananda Malik ◽  
Ayan Mukherjee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Cell Lines ◽  
Embryonic Stem

In vitro recapitulation of the urea cycle using murine embryonic stem cell-derived in vitro liver model

Amino Acids ◽  
2013 ◽  
Vol 45 (6) ◽  
pp. 1343-1351 ◽  
Author(s):  
Miho Tamai ◽  
Mami Aoki ◽  
Akihito Nishimura ◽  
Koji Morishita ◽  
Yoh-ichi Tagawa
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Urea Cycle ◽  
Embryonic Stem ◽  
Murine Embryonic Stem Cell ◽  
Liver Model

In vitro assessing the risk of drug-induced cardiotoxicity by embryonic stem cell-based biosensor

2011 ◽  
Vol 155 (1) ◽  
pp. 214-219 ◽  
Author(s):  
Qingjun Liu ◽  
Hui Yu ◽  
Zhou Tan ◽  
Hua Cai ◽  
Weiwei Ye ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Drug Induced

In vitro differentiation of retinal ganglion-like cells from embryonic stem cell derived neural progenitors

2009 ◽  
Vol 380 (2) ◽  
pp. 230-235 ◽  
Author(s):  
Balusamy Jagatha ◽  
Mundackal S. Divya ◽  
Rajendran Sanalkumar ◽  
Chandrasekharan L. Indulekha ◽  
Sasidharan Vidyanand ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Neural Progenitors ◽  
Retinal Ganglion ◽  
In Vitro Differentiation

scholarly journals In vitro and in vivo analyses of human embryonic stem cell-derived dopamine neurons

2005 ◽  
Vol 92 (5) ◽  
pp. 1265-1276 ◽  
Author(s):  
Chang-Hwan Park ◽  
Yang-Ki Minn ◽  
Ji-Yeon Lee ◽  
Dong Ho Choi ◽  
Mi-Yoon Chang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Dopamine Neurons

Assessment of the ultrastructural and proliferative properties of human embryonic stem cell-derived cardiomyocytes

2003 ◽  
Vol 285 (6) ◽  
pp. H2355-H2363 ◽  
Author(s):  
Mirit Snir ◽  
Izhak Kehat ◽  
Amira Gepstein ◽  
Raymond Coleman ◽  
Joseph Itskovitz-Eldor ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Late Stage ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Es Cell ◽  
Cardiomyocyte Proliferation ◽  
Ki 67

Assessment of early ultrastructural development and cell-cycle regulation in human cardiac tissue is significantly hampered by the lack of a suitable in vitro model. Here we describe the possible utilization of human embryonic stem cell (ES) lines for investigation of these processes. With the use of the embryoid body (EB) differentiation system, human ES cell-derived cardiomyocytes at different developmental stages were isolated and their histomorphometric, ultrastructural, and proliferative properties were characterized. Histomorphometric analysis revealed an increase in cell length, area, and length-to-width ratio in late-stage EBs (>35 days) compared with early (10–21 days) and intermediate (21–35 days) stages. This was coupled with a progressive ultrastructural development from an irregular myofibrillar distribution to an organized sarcomeric pattern. Cardiomyocyte proliferation, assessed by double labeling with cardiac-specific antibodies and either [3H]thymidine incorporation or Ki-67 immunolabeling, demonstrated a gradual withdrawal from cell cycle. Hence, the percentage of positively stained nuclei in early-stage cardiomyocytes ([3H]thymidine: 60 ± 10%, Ki-67: 54 ± 23%) decreased to 36 ± 7% and 9 ± 16% in intermediate-stage EBs and to <1% in late-stage cardiomyocytes. In conclusion, a reproducible temporal pattern of early cardiomyocyte proliferation, cell-cycle withdrawal, and ultrastructural maturation was noted in this model. Establishment of this unique in vitro surrogate system may allow to examine the molecular mechanisms underlying these processes and to assess interventions aiming to modify these properties. Moreover, the detailed characterization of the ES cell-derived cardiomyocyte may be crucial for the development of future cell replacement strategies aiming to regenerate functional myocardium.

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