Detailed analysis of public RNAseq data and long non-coding RNA: a proposed enhancement to mesenchymal stem cell characterisation

AbstractThe development of RNA sequencing (RNAseq) and corresponding emergence of public datasets have created new avenues of transcriptional marker search. The long non-coding RNAs (lncRNAs) constitute an emerging class of transcripts with a potential for high tissue specificity and function. Using a dedicated bioinformatics pipeline, we propose to construct a cell-specific catalogue of unannotated lncRNAs and to identify the strongest cell markers. This pipeline uses ab initio transcript identification, pseudoalignment and new methodologies such as a specific k-mer approach for naive quantification of expression in numerous RNAseq data.For an application model, we focused on Mesenchymal Stem Cells (MSCs), a type of adult multipotent stem-cells of diverse tissue origins. Frequently used in clinics, these cells lack extensive characterisation. Our pipeline was able to highlight different lncRNAs with high specificity for MSCs. In silico methodologies for functional prediction demonstrated that each candidate represents one specific state of MSCs biology. Together, these results suggest an approach that can be employed to harness lncRNA as cell marker, showing different candidates as potential actors in MSCs biology, while suggesting promising directions for future experimental investigations.

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Long non-coding RNA exploration for mesenchymal stem cell characterisation

BMC Genomics ◽

10.1186/s12864-020-07289-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Sébastien Riquier ◽

Marc Mathieu ◽

Chloé Bessiere ◽

Anthony Boureux ◽

Florence Ruffle ◽

...

Keyword(s):

Stem Cells ◽

Experimental Investigations ◽

Bioinformatics Pipeline ◽

Multipotent Stem Cells ◽

Non Coding Rna ◽

Rnaseq Data ◽

A Cell ◽

New Methodologies ◽

Public Datasets ◽

And Function

Abstract Background The development of RNA sequencing (RNAseq) and the corresponding emergence of public datasets have created new avenues of transcriptional marker search. The long non-coding RNAs (lncRNAs) constitute an emerging class of transcripts with a potential for high tissue specificity and function. Therefore, we tested the biomarker potential of lncRNAs on Mesenchymal Stem Cells (MSCs), a complex type of adult multipotent stem cells of diverse tissue origins, that is frequently used in clinics but which is lacking extensive characterization. Results We developed a dedicated bioinformatics pipeline for the purpose of building a cell-specific catalogue of unannotated lncRNAs. The pipeline performs ab initio transcript identification, pseudoalignment and uses new methodologies such as a specific k-mer approach for naive quantification of expression in numerous RNAseq data. We next applied it on MSCs, and our pipeline was able to highlight novel lncRNAs with high cell specificity. Furthermore, with original and efficient approaches for functional prediction, we demonstrated that each candidate represents one specific state of MSCs biology. Conclusions We showed that our approach can be employed to harness lncRNAs as cell markers. More specifically, our results suggest different candidates as potential actors in MSCs biology and propose promising directions for future experimental investigations.

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The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms22052472 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2472

Author(s):

Carl Randall Harrell ◽

Valentin Djonov ◽

Vladislav Volarevic

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Immune Cells ◽

Tissue Repair ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Multipotent Stem Cells ◽

Tissue Repair And Regeneration ◽

Almost All ◽

And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

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Long non-coding RNA HULC affects the proliferation, apoptosis, migration, and invasion of mesenchymal stem cells

Experimental Biology and Medicine ◽

10.1177/1535370218804781 ◽

2018 ◽

Vol 243 (13) ◽

pp. 1074-1082 ◽

Cited By ~ 4

Author(s):

Xiujun Li ◽

Jiali Wang ◽

Yuchen Pan ◽

Yujun Xu ◽

Dan Liu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Cancer ◽

Clinical Application ◽

Molecular Mechanisms ◽

Migration And Invasion ◽

Therapeutic Effects ◽

Non Coding Rna ◽

And Function ◽

Long Non Coding Rna

Further studies on the molecular mechanisms of mesenchymal stem cells in the maintenance of growth and function are essential for their clinical application. Growing evidence has shown that long non-coding RNAs (lncRNAs) play an important role in the regulation of mesenchymal stem cells. Recently, it is reported that highly upregulated in liver cancer (HULC), with another lncRNA MALAT-1, accelerated liver cancer stem cell growth. The regulating role of MALAT-1 in mesenchymal stem cells has been investigated. However, the effects of HULC on the mesenchymal stem cells are unknown. In this study, we overexpressed HULC in mesenchymal stem cells derived from umbilical cord and analyzed the cell phenotypes, proliferation, apoptosis, migration, invasion and differentiation of mesenchymal stem cells. We found that overexpression of HULC significantly promotes cell proliferation through promoting cell division and inhibits cell apoptosis. HULC-overexpressed mesenchymal stem cells migrate and invade faster than control mesenchymal stem cells. HULC has no effect on phenotypes and differentiation of mesenchymal stem cells. Furthermore, we found that the expression of HULC in mesenchymal stem cells could be reduced by several inflammatory factors, including TNF-α, TGF-β1, and R848. Taken together, our data demonstrated that HULC has a vital role in the growth and function maintenance of mesenchymal stem cells without affecting differentiation. Impact statement Exploring the molecular mechanisms of growth and function in MSCs is the key to improve their clinical therapeutic effects. Currently, more and more evidence show that the long non-coding RNA (lncRNA) plays an important role in the growth, stemness and function of MSCs.Both HULC and MALAT1 are the earliest discovered LNCRNAs, which are closely related to tumor growth. All of them can promote the growth of liver cancer stem cells. Previously, we have studied the effects of MALAT1 on the growth and function of MSCs. In this study, we focused on the effects of HULC on MSCs. We elucidated the effects of HULC on the growth and differentiation of MSCs, and explored the relationship between inflammatory stimuli and HULC expression in MSCs. Our findings provide a new molecular target for the growth and clinical application of MSCs.

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Msps Governs Acentrosomal Microtubule Assembly and Reactivation of Quiescent Neural Stem Cells

10.1101/2020.01.24.918227 ◽

2020 ◽

Author(s):

Qiannan Deng ◽

Ye Sing Tan ◽

Liang Yuh Chew ◽

Hongyan Wang

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Cell Body ◽

Microtubule Assembly ◽

Dependent Manner ◽

Contact Points ◽

A Cell ◽

And Function ◽

Cellular Protrusion ◽

E Cadherin

SUMMARYThe ability of stem cells to switch between quiescence and proliferation is crucial for tissue homeostasis and regeneration. Drosophila quiescent neural stem cells (NSCs) extend a primary cellular protrusion from the cell body prior to their reactivation. However, the structure and function of this protrusion are not well established. In this study, we show that in the primary protrusion of quiescent NSCs microtubules are predominantly acentrosomal and oriented plus-end-out, distal to the cell body. We have identified Mini Spindles (Msps)/XMAP215 as a key regulator of NSC reactivation and acentrosomal microtubule assembly in quiescent NSCs. We show that E-cadherin, a cell adhesion molecule, is localized to NSC-neuropil contact points, in a Msps-dependent manner, and is intrinsically required for NSC reactivation. Our study demonstrates a novel mechanism by which Msps-dependent microtubule assembly in the primary protrusion of quiescent NSCs targets E-cadherin to NSC-neuropil contact sites to promote NSC reactivation. We propose that the neuropil functions as a new niche for promoting NSC reactivation, which may be a general paradigm in mammalian systems.

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Mesenchymal Stem Cell: A Friend or Foe in Anti-Tumor Immunity

International Journal of Molecular Sciences ◽

10.3390/ijms222212429 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12429

Author(s):

Carl Randall Harrell ◽

Ana Volarevic ◽

Valentin G. Djonov ◽

Nemanja Jovicic ◽

Vladislav Volarevic

Keyword(s):

Stem Cells ◽

Tumor Microenvironment ◽

Tumor Cells ◽

Tumor Immunity ◽

Immune Cells ◽

Therapeutic Potential ◽

Current Knowledge ◽

Cellular Mechanisms ◽

Multipotent Stem Cells ◽

And Function

Mesenchymal stem cells (MSCs) are self-renewable, multipotent stem cells that regulate the phenotype and function of all immune cells that participate in anti-tumor immunity. MSCs modulate the antigen-presenting properties of dendritic cells, affect chemokine and cytokine production in macrophages and CD4+ T helper cells, alter the cytotoxicity of CD8+ T lymphocytes and natural killer cells and regulate the generation and expansion of myeloid-derived suppressor cells and T regulatory cells. As plastic cells, MSCs adopt their phenotype and function according to the cytokine profile of neighboring tumor-infiltrated immune cells. Depending on the tumor microenvironment to which they are exposed, MSCs may obtain pro- and anti-tumorigenic phenotypes and may enhance or suppress tumor growth. Due to their tumor-homing properties, MSCs and their exosomes may be used as vehicles for delivering anti-tumorigenic agents in tumor cells, attenuating their viability and invasive characteristics. Since many factors affect the phenotype and function of MSCs in the tumor microenvironment, a better understanding of signaling pathways that regulate the cross-talk between MSCs, immune cells and tumor cells will pave the way for the clinical use of MSCs in cancer immunotherapy. In this review article, we summarize current knowledge on the molecular and cellular mechanisms that are responsible for the MSC-dependent modulation of the anti-tumor immune response and we discuss different insights regarding therapeutic potential of MSCs in the therapy of malignant diseases.

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Distribution of GFRA1-expressing spermatogonia in adult mouse testis

Reproduction ◽

10.1530/rep-11-0385 ◽

2012 ◽

Vol 143 (3) ◽

pp. 325-332 ◽

Cited By ~ 63

Author(s):

Margherita Grasso ◽

Andrea Fuso ◽

Lisa Dovere ◽

Dirk G de Rooij ◽

Mario Stefanini ◽

...

Keyword(s):

Stem Cells ◽

Adult Mouse ◽

Pcr Analysis ◽

Seminiferous Tubules ◽

Self Renewal ◽

Expression Of Genes ◽

Specific Manner ◽

A Cell ◽

And Function ◽

Type A Spermatogonia

In mice and other mammals, spermatogenesis is maintained by spermatogonial stem cells (SSCs), a cell population belonging to undifferentiated type A spermatogonia. In the accepted model of SSC self-renewal, Asingle (As) spermatogonia are the stem cells, whereas paired (Apaired (Apr)) and chained (Aaligned (Aal)) undifferentiated spermatogonia are committed to differentiation. This model has been recently challenged by evidence that As and chained (Apr and Aal), undifferentiated spermatogonia are heterogeneous in terms of gene expression and function. The expression profile of several markers, such as GFRA1 (the GDNF co-receptor), is heterogeneous among As, Apr and Aal spermatogonia. In this study, we have analysed and quantified the distribution of GFRA1-expressing cells within the different stages of the seminiferous epithelial cycle. We show that in all stages, GFRA1+ chained spermatogonia (Apr to Aal) are more numerous than GFRA1+ As spermatogonia. Numbers of chained GFRA1+ spermatogonia are sharply reduced in stages VII–VIII when Aal differentiate into A1 spermatogonia. GFRA1 expression is regulated by GDNF and in cultures of isolated seminiferous tubules, we found that GDNF expression and secretion by Sertoli cells is stage-dependent, being maximal in stages II–VI and decreasing thereafter. Using qRT-PCR analysis, we found that GDNF regulates the expression of genes such as Tex14, Sohlh1 and Kit (c-Kit) known to be involved in spermatogonial differentiation. Expression of Kit was upregulated by GDNF in a stage-specific manner. Our data indicate that GDNF, besides its crucial role in the self-renewal of stem cells also functions in the differentiation of chained undifferentiated spermatogonia.

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