A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S]

Billing, Anja M.; Dib, Shaima S.; Bhagwat, Aditya; Silva, Israel Tojal da; Drummond, Rodrigo Duarte; Hayat, Shahina; Al-Mismar, Rasha; Ben-Hamidane, Hisham; Goswami, Neha; Engholm-Keller, Kasper; Larsen, Martin R.; Suhre, Karsten; Rafii, Arash; Graumann, Johannes

doi:10.1074/mcp.ra119.001356

Cited by 13 publications

(8 citation statements)

References 74 publications

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“…Cyclin D1 (encoded by CCND1 ) enhances the aggressive nature of CSCs by promoting cellular epithelial to mesenchymal transition (EMT), migration, proliferation, and drug resistance 24 . In addition, previous findings have highlighted RAF1 as a top promoter of mesenchymal stem cell (MSC) function 25 . MSCs have self‐renewing, secretory, and immunomodulatory (immune dampening) capabilities 25 and are known to regulate CSCs through paracrine mechanisms 26 .…”

Section: Discussionmentioning

confidence: 99%

“…In addition, previous findings have highlighted RAF1 as a top promoter of mesenchymal stem cell (MSC) function 25 . MSCs have self‐renewing, secretory, and immunomodulatory (immune dampening) capabilities 25 and are known to regulate CSCs through paracrine mechanisms 26 . Stat5b (encoded by STAT5B ) has been characterized to induce EMT and stem‐like properties via Jak2‐Stat5a/b signalingy 27 .…”

Section: Discussionmentioning

confidence: 99%

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Identifying a molecular profile to predict the risk of recurrence in high‐intermediate risk endometrial cancer

et al. 2021

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BackgroundPatients with high‐intermediate risk endometrial cancer (H‐IR EMCA) have an elevated risk of recurrence compared to low‐risk counterparts. Many H‐IR EMCA patients are treated with radiation or chemotherapy, but their overall survival is not significantly impacted by treatment. The objective of this study was to compare molecular profiles of H‐IR EMCA patients with disease recurrence to those without to identify characteristics that could better predict patient outcomes.MethodsTissue was acquired from H‐IR EMCA patients with disease recurrence (n=15) and without disease recurrence (n=15) who had not received adjuvant therapy and performed DNA and RNA analyses.ResultsIn recurrent population, 5 patients had matchingrecurrent and initial tumor tissues. Of note, 5/7 (71%) African Americanpatients had disease recurrence compared to 10/23 (43%) White patients. Inaddition, several new mutations were found in individual patient’s recurrentcompared to initial tumors.ConclusionsCurrently the treatment ofendometrial cancer is rapidly changing with molecular profiling becoming partof the standard of care. Additionally, it and is being incorporated intoclinical trials in this group of patients. The specific gene mutations and RNAexpression signatures that were observed in our small cohort need to bevalidated in larger cohorts to determine their impact.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identifying a molecular profile to predict the risk of recurrence in high‐intermediate risk endometrial cancer

et al. 2021

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“…In particular, the mouse ESC dataset ( Yang et al , 2019 ) (PRIDE: PXD010621), the human glioblastoma dataset ( Recasens et al , 2021 ) (PRIDE: PXD020441) and the mouse adipocyte dataset ( Su et al , 2019 ) (PRIDE: PXD011525) are used for evaluating the stability of selected SPSs. The human ESC dataset ( Billing et al , 2019 ) (PRIDE: PXD004652), the HCT116 dataset ( Hahn et al , 2021 ) (PRIDE: PXD023703), the T-cell dataset ( Martinez-Fabregas et al , 2020 ) (PRIDE: PXD020964) and the AGS cell dataset ( Yin et al , 2020 ) (PRIDE: PXD005093) are included for independent validation of the reproducibility of the proposed framework. All other human phosphoproteomic datasets were curated from the qPhos database ( Yu et al , 2019 , http://qphos.cancerbio.info ) and its updated version ( http://qptm.omicsbio.info ).…”

Section: Methodsmentioning

confidence: 99%

Functional analysis of the stable phosphoproteome reveals cancer vulnerabilities

Xiao¹,

Kim

Pang

et al. 2022

Bioinformatics

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Motivation The advance of mass spectrometry-based technologies enabled the profiling of the phosphoproteomes of a multitude of cell and tissue types. However, current research primarily focused on investigating the phosphorylation dynamics in specific cell types and experimental conditions, whereas the phosphorylation events that are common across cell/tissue types and stable regardless of experimental conditions are, so far, mostly ignored. Results Here, we developed a statistical framework to identify the stable phosphoproteome across 53 human phosphoproteomics datasets, covering 40 cell/tissue types and 194 conditions/treatments. We demonstrate that the stably phosphorylated sites (SPSs) identified from our statistical framework are evolutionarily conserved, functionally important, and enriched in a range of core signalling and gene pathways. Particularly, we show that SPSs are highly enriched in the RNA splicing pathway, an essential cellular process in mammalian cells, and frequently disrupted by cancer mutations, suggesting a link between the dysregulation of RNA splicing and cancer development through mutations on SPSs. Availability The source code for data analysis in this study is available from Github repository https://github.com/PYangLab/SPSs under the open-source license of GPL-3. The data used in this study are publicly available (see section ‘Data availability’). Supplementary information Supplementary data are available at Bioinformatics online.

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“…This finding indicated that NEAT1 could promote the differentiation of NB4 cells (Zeng et al, 2014). In addition, NEAT1 increased during the differentiation of many kinds of cells, including embryonic stem cells, muscle cells, nerve cells, and glial cells (Lehnert et al, 2007;Mercer et al, 2010;Billing et al, 2019;Cui et al, 2019;Wang et al, 2019). NEAT1 has been shown to be highly expressed in hematopoietic stem cells, progenitors, and immune cells.…”

Section: Introductionmentioning

confidence: 90%

Downregulation of Long Non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 Inhibits MEG-01 Differentiation and Platelet-Like Particles Activity

et al. 2020

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Platelets are derived from megakaryocytes and play an important role in blood coagulation. By using high throughput sequencing, we have found that the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) is abundant in platelets (GEO ID: 200097348). However, little is known about its role in regulating megakaryocyte differentiation and platelet activity. This study aims to clarify the effect of NEAT1 on MEG-01 differentiation and platelet-like particle (PLP) activity. NEAT1 in MEG-01 cells was knocked down by siRNA transfection. The adhesion of MEG-01 and PLP to collagen-coated coverslips was observed under a fluorescence microscope. Flow cytometry was used to investigate cell apoptosis, cell cycle, the levels of D41/CD42b on MEG-01 cells and CD62P on PLPs. Quantitative real-time polymerase chain reaction was used to detect NEAT1 and IL-8 expression levels. Western blot was used to measure the protein levels of Bcl-2, Bax, cleaved caspase-3, and IL-8. RNA-binding protein immunoprecipitation was used to detect the interaction of NEAT1 and splicing factor proline/glutamine-rich (SFPQ). Results showed that NEAT1 knockdown decreased the adhesion ability of thrombinstimulated MEG-01 and PLP. The expression of CD62P on PLPs and CD41/CD42b on MEG-01 cells was inhibited by NEAT1 knockdown. In addition, NEAT1 knockdown inhibited cell apoptosis with increased Bcl2/Bax ratio and decreased cleaved caspase-3, and reduced the percentage of cells in the G0/G1 phase. Meanwhile, NEAT1 knockdown inhibited the expression of IL-8. A strong interaction of NEAT1 and SFPQ, a transcriptional repressor of IL-8, was identified. NEAT1 knockdown reduced the interaction between SFPQ and NEAT1.The results suggest that lncRNA NEAT1 knockdown decreases MEG-01 differentiation, PLP activity, and IL-8 level. The results also indicate that the regulation of NEAT1 on IL-8 may be realized via a direct interaction between NEAT1 and SFPQ.

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A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S]

Cited by 13 publications

References 74 publications

Identifying a molecular profile to predict the risk of recurrence in high‐intermediate risk endometrial cancer

Identifying a molecular profile to predict the risk of recurrence in high‐intermediate risk endometrial cancer

Functional analysis of the stable phosphoproteome reveals cancer vulnerabilities

Downregulation of Long Non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 Inhibits MEG-01 Differentiation and Platelet-Like Particles Activity

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