An Insight Into the Whole Transcriptome Profile of Four Tissue-Specific Human Mesenchymal Stem Cells

Alhattab, Dana; Jamali, Fatima; Ali, Dema; Hammad, Hana; Adwan, Sofia; Rahmeh, Reem; Samarah, Omar Q.; Salah, Bareqa; Hamdan, Mohammad; Awidi, Abdalla

doi:10.2217/rme-2018-0137

Cited by 23 publications

(25 citation statements)

References 72 publications

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“…To provide insights into the heterogeneity of MSCs, several previous studies have compared gene expression of MSCs isolated from different sources using bulk-cell transcriptomic profiles (Alhattab et al, 2019; Fong et al, 2011; Lee et al, 2004; Ma et al, 2019; Meng et al, 2019; Taşkiran and Karaosmanoğlu, 2019). However, even MSCs derived from the same tissue exhibited inter-population functional heterogeneity, such as different differentiation potency and proliferation capacity.…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA-seq highlights heterogeneity in human primary Wharton’s Jelly mesenchymal stem/stromal cells cultured in vitro

Sun

Wang

et al. 2019

Preprint

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SUMMARYMesenchymal Stem/Stromal cells (MSCs) are multipotent cells with promising application potential in regenerative medicine and immunomodulation. However, MSCs cultured in vitro exhibit functional heterogeneity. The underlying molecular mechanisms that define MSC heterogeneity remain unclear. Here, we investigated gene-expression heterogeneity of human primary Wharton’s Jelly-derived MSCs (WJMSCs) cultured in vitro via single-cell RNA-seq. At the single-cell level, highly variable genes (HVGs) are associated with functional characteristics of classic MSCs. Differentially expressed genes analysis revealed the existence of several distinct subpopulations exhibit different functional characteristics associated with proliferation, development, and inflammation response. By comparing our WJMSCs data with a public available adipose-derived MSCs (ADMSCs) single cell transcriptomic data, we found that HVGs from these two studies are largely overlapped and have similar functional enrichment. Taken together, these results suggested that these HVGs hold the potential to be used as candidate markers for further potency association studies.

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Section: Resultsmentioning

confidence: 99%

Single-cell RNA-seq highlights heterogeneity in human primary Wharton’s Jelly mesenchymal stem/stromal cells cultured in vitro

Sun

Wang

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…To provide insights into the heterogeneity of MSCs, several previous studies have compared gene expression of MSCs isolated from different sources using bulk-cell transcriptomic profiles [60][61][62][63][64][65]. However, even MSCs derived from the same tissue exhibited inter-population functional heterogeneity, such as different differentiation potency and proliferation capacity.…”

Section: Single-cell Transcriptome Comparison Between Wjmscs and Admscsmentioning

confidence: 99%

Single-cell RNA-seq highlights heterogeneity in human primary Wharton’s jelly mesenchymal stem/stromal cells cultured in vitro

Sun

Wang

et al. 2020

Stem Cell Res Ther

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Background: Mesenchymal stem/stromal cells (MSCs) are multipotent cells with a promising application potential in regenerative medicine and immunomodulation. However, MSCs cultured in vitro exhibit functional heterogeneity. The underlying molecular mechanisms that define MSC heterogeneity remain unclear. Methods:We investigated the gene expression profile via single-cell RNA sequencing (scRNA-seq) of human primary Wharton's jelly-derived MSCs (WJMSCs) cultured in vitro from three donors. We also isolated CD142 + and CD142 − WJMSCs based on scRNA-seq data and compared their proliferation capacity and "wound healing" potential in vitro. Meanwhile, we analyzed publicly available adipose-derived MSC (ADMSCs) scRNA-seq data and performed transcriptome comparison between WJMSCs and ADMSCs at the single-cell level.Results: GO enrichment analysis of highly variable genes (HVGs) obtained from WJMSCs revealed that these genes are significantly enriched in extracellular region with binding function, involved in developmental process, signal transduction, cell proliferation, etc. Pathway analysis showed that these HVGs are associated with functional characteristics of classic MSCs, such as inflammation mediated by chemokine and cytokine signaling, integrin signaling, and angiogenesis. After regressing out the batch and cell cycle effects, these HVGs were used for dimension reduction and clustering analysis to identify candidate subpopulations. Differentially expressed gene analysis revealed the existence of several distinct subpopulations of MSCs that exhibit diverse functional characteristics related to proliferation, development, and inflammation response. In line with our data, sorted CD142 + and CD142 − WJMSCs showed distinct proliferation capacity as well as "wound healing" potential. Although WJMSCs and ADMSCs were derived from different tissues and were displaying different differentiation potencies, their HVGs were largely overlapped and had similar functional enrichment. Conclusion: HVGs identified in MSCs are associated with classic MSC function. Regarding therapeutic potential, these genes are associated with functional characteristics, on which the MSC clinical application were theoretically based, such as development and inflammation response. Altogether, these HVGs hold the potential to be used as candidate markers for further potency association studies.

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“…blocking buffer overnight at 4 0 C with shaking followed by wahing with 0.1% Triton-X-100 in PBS three times for 5 minutes each. Next, cells were stained with secondary antibodies ( (40). A day before cells reached 80% con uency, monolayers were washed twice with PBS (pH= 7.4) and once with serum free media -SFM (DM-F12).…”

Section: 24immuno Uorescent Assay Of Cd133 Positive Populationmentioning

confidence: 99%

WITHDRAWN: Anti-Oncogenic Activities Exhibited By Secretomes Of Mesenchymal Stem Cells Are Mediated By Modulation Of KITLG and DKK1 Genes In Glioma Stem Cells.

Aslam

Abusharieh

Abuarqoub

et al. 2020

Preprint

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Abstract Background. Cancer stem cells (CSCs) use their stemness properties such as self renewal, toxicity, plasticity, and communication with the tumor microenvironment (TME) to perpetuate their lineage and survive chemotherapy. Learning how to interrupt the self renewal ability or modulate the interaction of CSCs with the TME signaling will dramatically improve therapeutic impact on patient’s remission. Anti-tumor properties of mesenchymal stem cells (MSCs) are currently under investigations and different approaches have been applied to gain beneficial effects However, different types of MSCs yielded different conflicting results. In order to investigate if different types of MSCs preconditioned in the same culture conditions can exert alike anti oncogenic effect on glioma stem cells, we planned this study. Methods. GSCs were isolated from U87 cell line by FACS cell sorter, characterized and established as gliospheres. Condition media from MSCs of Wharton Jelly (WJ-MSCs) and bone marrow (BM-MSCs) were harvested and used as treatments on glioshperes (3D) to investigate the effect on proliferation, invasion and self renewal properties of GSCs. Microarray analysis was used to determine the effect at molecular level. Specific human CSC gene arrays were applied to validate the findings of the microarray explicitly the pluripotency of the GSCs. Results. Our results from functional and molecular assays showed that condition media (CM) from both types of MSCs inhibited the metabolism by interrupting oxidative phosphorylation, arrested the cell cycle, induced cell differentiation, targeted the pluripotency and up-regulated the immune response in GSCs. Moreover , condition media from both types of MSCs significantly affected the same genes (KITLG and DKK1) causing a similar effect while using slightly different routes and signaling pathways signifying their individual effects.Conclusion.We conclude that mesenchymal stem cells possess antitumor properties and paracrine factors of mesenchymal stem cells in combination with anti-immune modalities can provide novel therapeutic targets for glioma treatment.

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An Insight Into the Whole Transcriptome Profile of Four Tissue-Specific Human Mesenchymal Stem Cells

Cited by 23 publications

References 72 publications

Single-cell RNA-seq highlights heterogeneity in human primary Wharton’s Jelly mesenchymal stem/stromal cells cultured in vitro

Single-cell RNA-seq highlights heterogeneity in human primary Wharton’s Jelly mesenchymal stem/stromal cells cultured in vitro

Single-cell RNA-seq highlights heterogeneity in human primary Wharton’s jelly mesenchymal stem/stromal cells cultured in vitro

WITHDRAWN: Anti-Oncogenic Activities Exhibited By Secretomes Of Mesenchymal Stem Cells Are Mediated By Modulation Of KITLG and DKK1 Genes In Glioma Stem Cells.

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