Proteome Analysis of Ground State Pluripotency

Taleahmad, Sara; Mirzaei, Mehdi; Parker, Lindsay M.; Hassani, Seyedeh‐Nafiseh; Mollamohammadi, Sepideh; Sharifi-Zarchi, Ali; Haynes, Paul A.; Baharvand, Hossein; Salekdeh, Ghasem Hosseini

doi:10.1038/srep17985

Cited by 23 publications

(24 citation statements)

References 43 publications

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“…There are more than 20000 kinds of proteins in serum, which can reflect the serological changes of different stages for different diseases [ 22 – 25 ] . Using proteomics technology to screening specific proteins can provide new ideas and methods for the early diagnosis, treatment and prognosis of diseases.…”

Section: Discussionmentioning

confidence: 99%

Exploration of Serum Proteomic Profiling and Diagnostic Model That Differentiate Crohn's Disease and Intestinal Tuberculosis

Zhang

Ning

et al. 2016

PLoS ONE

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AimTo explore the diagnostic models of Crohn’s disease (CD), Intestinal tuberculosis (ITB) and the differential diagnostic model between CD and ITB by analyzing serum proteome profiles.MethodsSerum proteome profiles from 30 CD patients, 21 ITB patients and 30 healthy controls (HCs) were analyzed by using weak cationic magnetic beads combined with MALDI-TOF-MS technique to detect the differentially expressed proteins of serum samples. Three groups were made and compared accordingly: group of CD patients and HCs, group of ITB patients and HCs, group of CD patients and ITB patients. Wilcoxon rank sum test was used to screen the ten most differentiated protein peaks (P < 0.05). Genetic algorithm combining with support vector machine (SVM) was utilized to establish the optimal diagnostic models for CD, ITB and the optimal differential diagnostic model between CD and ITB. The predictive effects of these models were evaluated by Leave one out (LOO) cross validation method.ResultsThere were 236 protein peaks differently expressed between group of CD patients and HCs, 305 protein peaks differently expressed between group of ITB patients and HCs, 332 protein peaks differently expressed between group of CD patients and ITB patients. Ten most differentially expressed peaks were screened out between three groups respectively (P < 0.05) to establish diagnostic models and differential diagnostic model. A diagnostic model comprising of four protein peaks (M/Z 4964, 3029, 2833, 2900) can well distinguish CD patients and HCs, with a specificity and sensitivity of 96.7% and 96.7% respectively. A diagnostic model comprising four protein peaks (M/Z 3030, 2105, 2545, 4210) can well distinguish ITB patients and HCs, with a specificity and sensitivity of 93.3% and 95.2% respectively. A differential diagnostic model comprising three potential biomarkers protein peaks (M/Z 4267, 4223, 1541) can well distinguish CD patients and ITB patients, with a specificity and sensitivity of 76.2% and 80.0% respectively. Among the eleven protein peaks from the diagnostic models and differential diagnostic model, two have been successfully purified and identified, Those two peaks were M/Z 2900 from the diagnostic model between CD and HCs and M/Z 1541 from the differential diagnostic model between CD and ITB. M/Z 2900 was identified as appetite peptide, M/Z 1541 was identified as Lysyl oxidase-like 2 (LOXL-2).ConclusionThe differently expressed protein peaks analyzed by serum proteome with weak cationic magnetic beads combined MALDI-TOF-MS technique can effectively distinguish CD patients and HCs, ITB patients and HCs, CD patients and ITB patients. The diagnostic model between CD patients and HCs consisting of four protein peaks (M/Z 4964, 3029, 2833, 2900), the diagnostic model between ITB patients and HCs comprising four protein peaks (M/Z 3030, 2105, 2545, 4210) and the differential diagnostic model between CD patients and ITB patients comprising three protein peaks (M/Z 4267, 4223, 1541) had high specificity and sensitivity and can contribute to diag...

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Section: Discussionmentioning

confidence: 99%

Exploration of Serum Proteomic Profiling and Diagnostic Model That Differentiate Crohn's Disease and Intestinal Tuberculosis

Zhang

Ning

et al. 2016

PLoS ONE

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“…Interestingly, when mESCs adapted from serum to 2i conditions, the glycolysis pathway was significantly upregulated as detected by RNA-seq ( Marks et al., 2012 ). Similarly, protein levels of glycolysis enzymes are significantly increased in naive ESCs compared with ESCs cultured in serum ( Taleahmad et al., 2015 ). Our data further demonstrate that the downregulation of glycolysis by lncenc1 depletion impairs self-renewal, which suggests that a high level of glycolysis is vital for naive ESCs.…”

Section: Discussionmentioning

confidence: 99%

The Long Noncoding RNA Lncenc1 Maintains Naive States of Mouse ESCs by Promoting the Glycolysis Pathway

Sun

Zhu

et al. 2018

Stem Cell Reports

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SummaryThe naive embryonic stem cells (nESCs) display unique characteristics compared with the primed counterparts, but the underlying molecular mechanisms remain elusive. Here we investigate the functional roles of Lncenc1, a highly abundant long noncoding RNA in nESCs. Knockdown or knockout of Lncenc1 in mouse nESCs leads to a significantly decreased expression of core pluripotency genes and a significant reduction of colony formation capability. Furthermore, upon the depletion of Lncenc1, the expression of glycolysis-associated genes is significantly reduced, and the glycolytic activity is substantially impaired, as indicated by a more than 50% reduction in levels of glucose consumption, lactate production, and extracellular acidification rate. Mechanistically, Lncenc1 interacts with PTBP1 and HNRNPK, which regulate the transcription of glycolytic genes, thereby maintaining the self-renewal of nESCs. Our results demonstrate the functions of Lncenc1 in linking energy metabolism and naive state of ESCs, which may enhance our understanding of the molecular basis underlying naive pluripotency.

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“…Also, the descriptive and predictive power of mathematical models could be significantly increased accounting also for the combined role of noncoding RNAs [96–99], epigenetic mechanisms [100], metabolism [101], and posttranscriptional modifications [102]. …”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Nanog Dynamics in Mouse Embryonic Stem Cells: Results from Systems Biology Approaches

Marucci

2017

Stem Cells International

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Mouse embryonic stem cells (mESCs), derived from the inner cell mass of the blastocyst, are pluripotent stem cells having self-renewal capability and the potential of differentiating into every cell type under the appropriate culture conditions. An increasing number of reports have been published to uncover the molecular mechanisms that orchestrate pluripotency and cell fate specification using combined computational and experimental methodologies. Here, we review recent systems biology approaches to describe the causes and functions of gene expression heterogeneity and complex temporal dynamics of pluripotency markers in mESCs under uniform culture conditions. In particular, we focus on the dynamics of Nanog, a key regulator of the core pluripotency network and of mESC fate. We summarize the strengths and limitations of different experimental and modeling approaches and discuss how various strategies could be used.

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Proteome Analysis of Ground State Pluripotency

Cited by 23 publications

References 43 publications

Exploration of Serum Proteomic Profiling and Diagnostic Model That Differentiate Crohn's Disease and Intestinal Tuberculosis

Exploration of Serum Proteomic Profiling and Diagnostic Model That Differentiate Crohn's Disease and Intestinal Tuberculosis

The Long Noncoding RNA Lncenc1 Maintains Naive States of Mouse ESCs by Promoting the Glycolysis Pathway

Nanog Dynamics in Mouse Embryonic Stem Cells: Results from Systems Biology Approaches

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