Dynamic post-transcriptional regulation during embryonic stem cell differentiation

Pr, van den Berg; Budnik, Bogdan; Slavov, Nikolai; Semrau, Stefan

doi:10.1101/123497

Cited by 15 publications

(14 citation statements)

References 46 publications

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“…Although differences in NANOG, OCT4A, and SOX2 mRNA expressions were detectable between the groups at different time points, only NANOG was detectable on protein level, in line with earlier reports on dissimilar NANOG, OCT4A, and SOX2 protein and mRNA expression dynamics within mesenchymal stem/progenitor cells [54][55][56]. This AA/retinol-induced increase in the NANOG, especially in the presence of controlled inflammatory stimuli at 3 days, could be ascribed primarily to the capability of AA and retinol to activate the ten-eleven translocation (TET) DNA demethylases, initiating intracellular epigenetic reprogramming with pluripotency amplification [20,57].…”

Section: Discussionsupporting

confidence: 91%

Ascorbic Acid/Retinol and/or Inflammatory Stimuli’s Effect on Proliferation/Differentiation Properties and Transcriptomics of Gingival Stem/Progenitor Cells

El‐Sayed

Bittner

Schlicht

et al. 2021

Cells

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The present study explored the effects of ascorbic-acid (AA)/retinol and timed inflammation on the stemness, the regenerative potential, and the transcriptomics profile of gingival mesenchymal stem/progenitor cells’ (G-MSCs). STRO-1 (mesenchymal stem cell marker) immuno-magnetically sorted G-MSCs were cultured in basic medium (control group), in basic medium with IL-1β (1 ng/mL), TNF-α (10 ng/mL) and IFN-γ (100 ng/mL, inflammatory-medium), in basic medium with AA (250 µmol/L) and retinol (20 µmol/L) (AA/retinol group) or in inflammatory medium with AA/retinol (inflammatory/AA/retinol group; n = 5/group). The intracellular levels of phosphorylated and total β-Catenin at 1 h, the expression of stemness genes over 7 days, the number of colony-forming units (CFUs) as well as the cellular proliferation aptitude over 14 days, and the G-MSCs’ multilineage differentiation potential were assessed. Next-generation sequencing was undertaken to elaborate on up-/downregulated genes and altered intracellular pathways. G-MSCs demonstrated all mesenchymal stem/progenitor cells characteristics. Controlled inflammation with AA/retinol significantly elevated NANOG (p < 0.05). The AA/retinol-mediated reduction in intracellular phosphorylated β-Catenin was restored through the effect of controlled inflammation (p < 0.05). Cellular proliferation was highest in the AA/retinol group (p < 0.05). AA/retinol counteracted the inflammation-mediated reduction in G-MSCs’ clonogenic ability and CFUs. Amplified chondrogenic differentiation was observed in the inflammatory/AA/retinol group. At 1 and 3 days, the differentially expressed genes were associated with development, proliferation, and migration (FOS, EGR1, SGK1, CXCL5, SIPA1L2, TFPI2, KRATP1-5), survival (EGR1, SGK1, TMEM132A), differentiation and mineral absorption (FOS, EGR1, MT1E, KRTAP1-5, ASNS, PSAT1), inflammation and MHC-II antigen processing (PER1, CTSS, CD74) and intracellular pathway activation (FKBP5, ZNF404). Less as well as more genes were activated the longer the G-MSCs remained in the inflammatory medium or AA/retinol, respectively. Combined, current results point at possibly interesting interactions between controlled inflammation or AA/retinol affecting stemness, proliferation, and differentiation attributes of G-MSCs.

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Section: Discussionsupporting

confidence: 91%

Ascorbic Acid/Retinol and/or Inflammatory Stimuli’s Effect on Proliferation/Differentiation Properties and Transcriptomics of Gingival Stem/Progenitor Cells

El‐Sayed

Bittner

Schlicht

et al. 2021

Cells

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“…While initial work focused on epigenetic mechanisms, we now appreciate that transcriptional events do not entirely determine cellular identity. Recent studies have revealed that diverse post-transcriptional mechanisms influence the functional output of genetic programs (i.e., proteome content) required by stem cells (Nilsen and Graveley, 2010;van den Berg et al, 2017;Williamson et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Post-Transcriptional Regulation of Homeostatic, Stressed, and Malignant Stem Cells

et al. 2020

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Cellular identity is not driven by differences in genomic content but rather by epigenomic, transcriptomic, and proteomic heterogeneity. Although regulation of the epigenome plays a key role in shaping stem cell hierarchies, differential expression of transcripts only partially explains protein abundance. The epitranscriptome, translational control, and protein degradation have emerged as fundamental regulators of proteome complexity that regulate stem cell identity and function. Here, we discuss how post-transcriptional mechanisms enable stem cell homeostasis and responsiveness to developmental cues and environmental stressors by rapidly shaping the content of their proteome and how these processes are disrupted in pre-malignant and malignant states. Poly(A)-binding protein (PABP) RNA-binding protein that binds to the poly(A) tail of eukaryotic mRNA eIF4 binding protein (4E-BP) binds and sequesters the cap-binding translation initiation factor eIF4E to suppress protein synthesis Ribosomopathies diseases that are associated with mutations in ribosomal genes ER unfolded protein response (UPR ER ) stress response pathway activated by the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum Mitochondrial unfolded protein response (UPR MT ) stress response pathway activated by the accumulation of unfolded/misfolded proteins in the mitochondria Heat shock response stress response pathway activated by the accumulation of unfolded/misfolded proteins in the cytoplasm Ubiquitin-proteasome system cellular protein degradation system in which proteins destined for degradation are ubiquitinated and degraded by the proteasome Cancer stem cells a subset of cancer cells that can self-renew and differentiate into cells that comprise the tumor, thus contributing to tumorigenesis

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“…This could be because of the alignment of the datasets or because of the different labeling procedures of the datasets. That is, the PBMC-FACS data was labeled based on the expression of cell surface markers instead of clustering the cells, and it is known that protein and gene expression poorly correlated [27,28], which might explain these results.…”

Section: Discussionmentioning

confidence: 99%

Hierarchical progressive learning of cell identities in single-cell data

Michielsen

Reinders

Mahfouz

2020

Preprint

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Motivation:In single-cell RNA-sequencing datasets, cell identification is mainly done manually, which is subjective and time-consuming. As a consequence, most datasets are annotated at a different resolution. This is not surprising as cell populations form a hierarchy, but it can be problematic for downstream analysis or comparison of datasets. Several supervised methods have been developed to overcome the drawbacks of unsupervised learning, but none of these combines the information of multiple datasets and preserves the old definition of the cell populations in each dataset. Results: To overcome these challenges, we developed a hierarchical progressive learning method which automatically finds relationships between populations of multiple datasets and uses this to construct a classification tree. We implemented the tree with a one-class and linear SVM for each node and evaluated the classification performance, including the rejection option, and tree construction. At the moment, choosing between a one-class and linear SVM is a trade-off between the ability of discovering new cell populations and a higher accuracy. Both the one-class and linear SVM also outperform other hierarchical classifiers. Furthermore, we show that it is possible to construct a correct classification tree for immune cells when combining three PBMC datasets and predict the labels of the fourth dataset with high accuracy.

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Dynamic post-transcriptional regulation during embryonic stem cell differentiation

Cited by 15 publications

References 46 publications

Ascorbic Acid/Retinol and/or Inflammatory Stimuli’s Effect on Proliferation/Differentiation Properties and Transcriptomics of Gingival Stem/Progenitor Cells

Ascorbic Acid/Retinol and/or Inflammatory Stimuli’s Effect on Proliferation/Differentiation Properties and Transcriptomics of Gingival Stem/Progenitor Cells

Post-Transcriptional Regulation of Homeostatic, Stressed, and Malignant Stem Cells

Hierarchical progressive learning of cell identities in single-cell data

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