scholarly journals Dynamic post-transcriptional regulation during embryonic stem cell differentiation

2017 ◽  
Author(s):  
Patrick R. van den Berg ◽  
Bogdan Budnik ◽  
Nikolai Slavov ◽  
Stefan Semrau
Keyword(s):  
Stem Cells ◽  
Transcriptional Regulation ◽  
Kinetic Model ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Specific Gene ◽  
Data Set ◽  
Protein Levels ◽  
Comprehensive Data ◽  
Post Transcriptional Regulation

SummaryDuring in vitro differentiation, pluripotent stem cells undergo extensive remodeling of their gene expression profile. While studied extensively at the transcriptome level, much less is known about protein dynamics. Here, we measured mRNA and protein levels of 7459 genes during differentiation of embryonic stem cells (ESCs). This comprehensive data set revealed pervasive discordance between mRNA and protein. The high temporal resolution of the data made it possible to determine protein turnover rates genome-wide by fitting a kinetic model. This model further enabled us to systematically identify dynamic post-transcriptional regulation. Moreover, we linked different modes of regulation to the function of specific gene sets. Finally, we showed that the kinetic model can be applied to singlecell transcriptomics data to predict protein levels in differentiated cell types. In conclusion, our comprehensive data set, easily accessible through a web application, is a valuable resource for the discovery of post-transcriptional regulation in ESC differentiation.

scholarly journals Quantitative Proteomics Analysis Demonstrates Post-transcriptional Regulation of Embryonic Stem Cell Differentiation to Hematopoiesis

2007 ◽  
Vol 7 (3) ◽  
pp. 459-472 ◽  
Author(s):  
Andrew J. K. Williamson ◽  
Duncan L. Smith ◽  
David Blinco ◽  
Richard D. Unwin ◽  
Stella Pearson ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Embryonic Stem Cell ◽  
Quantitative Proteomics ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Embryonic Stem Cell Differentiation ◽  
Proteomics Analysis ◽  
Post Transcriptional Regulation

Essential Cytoplasmic Role of the Histone Lysine Methyltransferase Setdb1 in Post-Transcriptional Regulation in Embryonic Stem Cells

2021 ◽  
Author(s):  
Roberta Rapone ◽  
Laurence Del Maestro ◽  
Costas Bouyioukos ◽  
Sonia Albini ◽  
Paola Cruz-Tapias ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Transcriptional Regulation ◽  
Mrna Stability ◽  
Regulation Of Gene Expression ◽  
Embryonic Stem ◽  
Histone Lysine ◽  
Histone Lysine Methyltransferase ◽  
Lysine Methyltransferase ◽  
Post Transcriptional Regulation

Abstract Embryonic stem cells (ESCs) fate is regulated both at transcriptional and post-transcriptional levels. Indeed, several studies showed that, in addition to gene transcription, mRNA stability and protein synthesis are finely tuned and strongly control the ESCs pluripotency and fate changes. An increasing number of RNA-binding proteins (RBPs) involved in post-transcriptional and translational regulation of gene expression has been identified as regulators of ESC identity. The major lysine methyltransferase Setdb1 is essential for the self-renewal and viability of ESCs. Setdb1 was primarily known to methylate the lysine 9 of histone 3 (H3K9) in the nucleus, where it regulates chromatin functions. However, Setdb1 is also massively localized in the cytoplasm, including in mouse ESCs, where its role remains unknown. Here we show that the cytoplasmic Setdb1 (cSetdb1) is essential for the survival of mESCs. Functional assays further demonstrate that cSetdb1 regulates gene expression post-transcriptionally, affecting the abundance of mRNAs and the rate of newly synthetized proteins. A yeast-two-hybrid assay shows that cSetdb1 interacts with several regulators of mRNA stability and protein translation machinery, such as the ESCs-specific E3 ubiquitin ligase and mRNA silencer Trim71/Lin41. Finally, proteomic analyses reveal that cSetdb1 is required for the integrity of Trim71 complexes involved in mRNA metabolism and translation. Altogether, our data uncover the essential cytoplasmic function of a firstly supposed nuclear “histone” lysine methyltransferase, Setdb1, and provide new insights into the cytoplasmic/post-transcriptional regulation of gene expression mediated by a key epigenetic regulator.

Abstract 3822: Different microRNA In Mouse Heart, Cardiac Stem Cells And Cardiac Stem Cells With GATA4, Indicate Different Sets Of microRNA Involved In Stem Cell Differentiation By Gene Repression

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Edilamar M de Oliveira ◽  
Yao Liang Tang ◽  
Keping Qian ◽  
leping Shen ◽  
Luvena Ong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Activin A ◽  
Specific Gene ◽  
Mouse Heart ◽  
Heart Cells ◽  
Cardiac Stem Cells

Several studies suggest that miRNA have important roles in the development of the heart and cardiac function. We hypothesized that specific miRNA are involved in the differentiation steps of cardiac stem cells to heart cells. We studied 569 unique miRNAs probes in mouse heart cells (MHtC), cardiac stem cells (CSC) and CSC with GATA4 (CSCG) . Based on Sanger miRMouse -10.1, we compared miRNAs in the following groups 1) MHtC vs. CSC, 2) CSC vs.CSCG , 3) MHtCs v CSCG. We also compared CSCs under hypoxia and normoxia. miRNAs reported in the results were confirmed by PCR As previously reported miRNA 1, 133a and 133b were highly expressed in MHt. However, we also found previously unreported, relatively high expression of miRNAs 126 –3p, 145, , 451and 499 in MHtC. MicroRNAs have not previously been reported in CSCs or CSCG. We found unique expression miRNAs 10a,10b, 31, 214 and 762 in CSCs and increased expression of miRNAs 705,709,762, and 1224 in CSCG. In MHt, miR 21 was lower compared to miR21 in CSCs . Expression of miRNA-762 was expressed significantly more in CSC-G than in CSC. Therefore, miR-762 could be the direct transcriptional target of GATA-4 in CSC and a part of the differentiation control pathway from CSC to MHtC. In addition we studied miRNA from CSCs exposed to hypoxia. Hypoxia suppressed all miRs found except miR-574 –5p, which was increased in hypoxia. The results led us to identify which genes are targeted by these miRNAs. miRNA 762 is located into the BCl-7c gene and by miRNA target predictions it was found to target activin A receptor (type IB and II-like-1) gene, bone morphogenic gene and transforming growth factor, beta receptor III (TGFβIII). Embryonic stem cells differentiate into cardiomyocytes in the presence of activin A and BMP4, therefore we suggest that the miRNA 700 family ( miR762 in particluar) in cardiac stem cells inhibits activin A and BMP4 genes, possibly through TGFβIII signaling, to maintain stem cells in the undifferentiated state. The results reveal new miRNAs in cardiac stem cells differentiation to adult heart cells and suggest their role of specific gene targeting.

scholarly journals Lin28-mediated post-transcriptional regulation of Oct4 expression in human embryonic stem cells

2009 ◽  
Vol 38 (4) ◽  
pp. 1240-1248 ◽  
Author(s):  
Caihong Qiu ◽  
Yinghong Ma ◽  
Jianquan Wang ◽  
Shuping Peng ◽  
Yingqun Huang
Keyword(s):  
Stem Cells ◽  
Transcriptional Regulation ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Oct4 Expression ◽  
Post Transcriptional Regulation

scholarly journals G-quadruplex DNA structures in human stem cells and differentiation

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Katherine G. Zyner ◽  
Angela Simeone ◽  
Sean M. Flynn ◽  
Colm Doyle ◽  
Giovanni Marsico ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Structural Features ◽  
Specific Gene ◽  
Human Stem Cells ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Stem Cell Pluripotency

AbstractThe establishment of cell identity during embryonic development involves the activation of specific gene expression programmes and is underpinned by epigenetic factors including DNA methylation and histone post-translational modifications. G-quadruplexes are four-stranded DNA secondary structures (G4s) that have been implicated in transcriptional regulation and cancer. Here, we show that G4s are key genomic structural features linked to cellular differentiation. We find that G4s are highly abundant in human embryonic stem cells and are lost during lineage specification. G4s are prevalent in enhancers and promoters. G4s that are found in common between embryonic and downstream lineages are tightly linked to transcriptional stabilisation of genes involved in essential cellular functions as well as transitions in the histone post-translational modification landscape. Furthermore, the application of small molecules that stabilise G4s causes a delay in stem cell differentiation, keeping cells in a more pluripotent-like state. Collectively, our data highlight G4s as important epigenetic features that are coupled to stem cell pluripotency and differentiation.

scholarly journals ARID4B is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit

2020 ◽  
Vol 295 (51) ◽  
pp. 17738-17751
Author(s):  
Nihal Terzi Cizmecioglu ◽  
Jialiang Huang ◽  
Ezgi G. Keskin ◽  
Xiaofeng Wang ◽  
Idil Esen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Critical Role ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Specific Gene ◽  
Embryonic Stem Cell Differentiation ◽  
Self Renewal ◽  
Cell Fate Decisions

Distinct cell types emerge from embryonic stem cells through a precise and coordinated execution of gene expression programs during lineage commitment. This is established by the action of lineage specific transcription factors along with chromatin complexes. Numerous studies have focused on epigenetic factors that affect embryonic stem cells (ESC) self-renewal and pluripotency. However, the contribution of chromatin to lineage decisions at the exit from pluripotency has not been as extensively studied. Using a pooled epigenetic shRNA screen strategy, we identified chromatin-related factors critical for differentiation toward mesodermal and endodermal lineages. Here we reveal a critical role for the chromatin protein, ARID4B. Arid4b-deficient mESCs are similar to WT mESCs in the expression of pluripotency factors and their self-renewal. However, ARID4B loss results in defects in up-regulation of the meso/endodermal gene expression program. It was previously shown that Arid4b resides in a complex with SIN3A and HDACS 1 and 2. We identified a physical and functional interaction of ARID4B with HDAC1 rather than HDAC2, suggesting functionally distinct Sin3a subcomplexes might regulate cell fate decisions Finally, we observed that ARID4B deficiency leads to increased H3K27me3 and a reduced H3K27Ac level in key developmental gene loci, whereas a subset of genomic regions gain H3K27Ac marks. Our results demonstrate that epigenetic control through ARID4B plays a key role in the execution of lineage-specific gene expression programs at pluripotency exit.

scholarly journals Modulation of Differentiation of Embryonic Stem Cells by Polypyrrole: The Impact on Neurogenesis

2021 ◽  
Vol 22 (2) ◽  
pp. 501
Author(s):  
Kateřina Skopalová ◽  
Katarzyna Anna Radaszkiewicz ◽  
Věra Kašpárková ◽  
Jaroslav Stejskal ◽  
Patrycja Bober ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Active Role ◽  
Low Molecular Weight ◽  
Conducting Materials ◽  
The Impact ◽  
Erk Kinase

The active role of biomaterials in the regeneration of tissues and their ability to modulate the behavior of stem cells in terms of their differentiation is highly advantageous. Here, polypyrrole, as a representantive of electro-conducting materials, is found to modulate the behavior of embryonic stem cells. Concretely, the aqueous extracts of polypyrrole induce neurogenesis within embryonic bodies formed from embryonic stem cells. This finding ledto an effort to determine the physiological cascade which is responsible for this effect. The polypyrrole modulates signaling pathways of Akt and ERK kinase through their phosphorylation. These effects are related to the presence of low-molecular-weight compounds present in aqueous polypyrrole extracts, determined by mass spectroscopy. The results show that consequences related to the modulation of stem cell differentiation must also be taken into account when polypyrrole is considered as a biomaterial.

scholarly journals RALYL increases hepatocellular carcinoma stemness by sustaining the mRNA stability of TGF-β2

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xia Wang ◽  
Jin Wang ◽  
Yu-Man Tsui ◽  
Chaoran Shi ◽  
Ying Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mrna Stability ◽  
Rna Binding ◽  
Embryonic Stem ◽  
Molecular Characteristics ◽  
Specific Gene ◽  
Functional Studies ◽  
Poor Differentiation ◽  
Development In Vitro

AbstractGrowing evidences suggest that cancer stem cells exhibit many molecular characteristics and phenotypes similar to their ancestral progenitor cells. In the present study, human embryonic stem cells are induced to differentiate into hepatocytes along hepatic lineages to mimic liver development in vitro. A liver progenitor specific gene, RALY RNA binding protein like (RALYL), is identified. RALYL expression is associated with poor prognosis, poor differentiation, and metastasis in clinical HCC patients. Functional studies reveal that RALYL could promote HCC tumorigenicity, self-renewal, chemoresistance, and metastasis. Moreover, molecular mechanism studies show that RALYL could upregulate TGF-β2 mRNA stability by decreasing N6-methyladenosine (m6A) modification. TGF-β signaling and the subsequent PI3K/AKT and STAT3 pathways, upregulated by RALYL, contribute to the enhancement of HCC stemness. Collectively, RALYL is a liver progenitor specific gene and regulates HCC stemness by sustaining TGF-β2 mRNA stability. These findings may inspire precise therapeutic strategies for HCC.

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