scholarly journals Exploration of Alternative Splicing Events in Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 737
Author(s):  
Ji-Eun Jeong ◽  
Binna Seol ◽  
Han-Seop Kim ◽  
Jae-Yun Kim ◽  
Yee-Sook Cho
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Alternative Splicing ◽  
Functional Enrichment ◽  
Actin Binding ◽  
Pcr Analysis ◽  
Valuable Insight ◽  
Sequencing Analysis ◽  
Induced Pluripotent ◽  
Insight Into

Although comparative genome-wide transcriptomic analysis has provided insight into the biology of human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs), the distinct alternative splicing (AS) signatures of iMSCs remain elusive. Here, we performed Illumina RNA sequencing analysis to characterize AS events in iMSCs compared with tissue-derived MSCs. A total of 4586 differentially expressed genes (|FC| > 2) were identified between iMSCs and umbilical cord blood-derived MSCs (UCB-MSCs), including 2169 upregulated and 2417 downregulated genes. Of these, 164 differentially spliced events (BF > 20) in 112 genes were identified between iMSCs and UCB-MSCs. The predominant type of AS found in iMSCs was skipped exons (43.3%), followed by retained introns (19.5%), alternative 3′ (15.2%) and 5′ (12.8%) splice sites, and mutually exclusive exons (9.1%). Functional enrichment analysis showed that the differentially spliced genes (|FC| > 2 and BF > 20) were mainly enriched in functions associated with focal adhesion, extracellular exosomes, extracellular matrix organization, cell adhesion, and actin binding. Splice isoforms of selected genes including TRPT1, CNN2, and AP1G2, identified in sashimi plots, were further validated by RT-PCR analysis. This study provides valuable insight into the biology of iMSCs and the translation of mechanistic understanding of iMSCs into therapeutic applications.

scholarly journals Mettl3 Regulates Osteogenic Differentiation and Alternative Splicing of Vegfa in Bone Marrow Mesenchymal Stem Cells

2019 ◽  
Vol 20 (3) ◽  
pp. 551 ◽  
Author(s):  
Cheng Tian ◽  
Yanlan Huang ◽  
Qimeng Li ◽  
Zhihui Feng ◽  
Qiong Xu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Alternative Splicing ◽  
Osteogenic Differentiation ◽  
Bone Repair ◽  
Bone Mineralization ◽  
Sequencing Analysis ◽  
Bone Mesenchymal Stem Cells ◽  
Vast Number

Bone mesenchymal stem cells (BMSCs) can be a useful cell resource for developing biological treatment strategies for bone repair and regeneration, and their therapeutic applications hinge on an understanding of their physiological characteristics. N6-methyl-adenosine (m6A) is the most prevalent internal chemical modification of mRNAs and has recently been reported to play important roles in cell lineage differentiation and development. However, little is known about the role of m6A modification in the cell differentiation of BMSCs. To address this issue, we investigated the expression of N6-adenosine methyltransferases (Mettl3 and Mettl14) and demethylases (Fto and Alkbh5) and found that Mettl3 was upregulated in BMSCs undergoing osteogenic induction. Furthermore, we knocked down Mettl3 and demonstrated that Mettl3 knockdown decreased the expression of bone formation-related genes, such as Runx2 and Osterix. The alkaline phosphatase (ALP) activity and the formation of mineralized nodules also decreased after Mettl3 knockdown. RNA sequencing analysis revealed that a vast number of genes affected by Mettl3 knockdown were associated with osteogenic differentiation and bone mineralization. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that the phosphatidylinositol 3-kinase/AKT (PI3K-Akt) signaling pathway appeared to be one of the most enriched pathways, and Western blotting results showed that Akt phosphorylation was significantly reduced after Mettl3 knockdown. Mettl3 has been reported to play an important role in regulating alternative splicing of mRNA in previous research. In this study, we found that Mettl3 knockdown not only reduced the expression of Vegfa but also decreased the level of its splice variants, vegfa-164 and vegfa-188, in Mettl3-deficient BMSCs. These findings might contribute to novel progress in understanding the role of epitranscriptomic regulation in the osteogenic differentiation of BMSCs and provide a promising perspective for new therapeutic strategies for bone regeneration.

Induced pluripotent stem cell-derived mesenchymal stem cells: A leap toward personalized therapies.

2016 ◽  
Vol 11 (2) ◽  
pp. 141-148 ◽  
Author(s):  
Jason Whitt ◽  
Krishna C. Vallabhaneni ◽  
Patrice Penfornis ◽  
Radhika Pochampally
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Induced Pluripotent

scholarly journals In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells

2021 ◽  
Vol 52 ◽  
pp. 102233
Author(s):  
Masayoshi Yoshimatsu ◽  
Hiroe Ohnishi ◽  
Chengzhu Zhao ◽  
Yasuyuki Hayashi ◽  
Fumihiko Kuwata ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neural Crest ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Neural Crest Cells ◽  
Laryngeal Cartilage ◽  
Induced Pluripotent

scholarly journals Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 42
Author(s):  
Xiaoyu Pu ◽  
Siyang Ma ◽  
Yan Gao ◽  
Tiankai Xu ◽  
Pengyu Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Radiation Damage ◽  
Therapeutic Potential ◽  
Damage Model ◽  
Bioactive Substances ◽  
Radiation Induced ◽  
Insight Into

Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage.

scholarly journals Proteomic Analysis of the Secretome and Exosomes of Feline Adipose-Derived Mesenchymal Stem Cells

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 295
Author(s):  
Antonio J. Villatoro ◽  
María del Carmen Martín-Astorga ◽  
Cristina Alcoholado ◽  
María del Mar Sánchez-Martín ◽  
José Becerra
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Endocrine System ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Junctions ◽  
Bioactive Molecules ◽  
Protein Protein Interaction ◽  
Cell Signaling Pathways

Mesenchymal stem cells (MSCs) have been shown to have therapeutic efficacy in different complex pathologies in feline species. This effect is attributed to the secretion of a wide variety of bioactive molecules and extracellular vesicles, such as exosomes, with significant paracrine activity, encompassed under the concept of the secretome. However, at present, the exosomes from feline MSCs have not yet been studied in detail. The objective of this study is to analyze and compare the protein profiles of the secretome as a whole and its exosomal fraction from feline adipose-derived MSCs (fAd-MSCs). For this, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein–Protein Interaction Networks Functional Enrichment Analysis (STRING) were utilized. A total of 239 proteins were identified in the secretome, and 228 proteins specific to exosomes were identified, with a total of 133 common proteins. The proteins identified in the secretome were located in the extracellular regions and in the cytoplasm, while the exosomal proteins were located mainly in the membrane, cytoplasm and cytosol. Regarding function, in the secretome, proteins involved in different metabolic pathways, in pathways related to the immune system and the endocrine system and in the processing of proteins in the endoplasmic reticulum predominated. In contrast, proteins specific to exosomes were predominantly associated with endocytosis, cell junctions, platelet activation and other cell signaling pathways. The possible future use of the secretome, or some of its components, such as exosomes, would provide a non-cell-based therapeutic strategy for the treatment of different diseases that would avoid the drawbacks of cell therapy.

scholarly journals Comparison of Human Induced Pluripotent Stem-Cell Derived Cardiomyocytes with Human Mesenchymal Stem Cells following Acute Myocardial Infarction

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e116281 ◽  
Author(s):  
Lucas Citro ◽  
Shan Naidu ◽  
Fatemat Hassan ◽  
M. Lakshmi Kuppusamy ◽  
Periannan Kuppusamy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Human Mesenchymal Stem Cells ◽  
Induced Pluripotent Stem Cell ◽  
Induced Pluripotent

An insight into non-integrative gene delivery approaches to generate transgene-free induced pluripotent stem cells

Gene ◽  
2019 ◽  
Vol 686 ◽  
pp. 146-159 ◽  
Author(s):  
Krishna Kumar Haridhasapavalan ◽  
Manash P. Borgohain ◽  
Chandrima Dey ◽  
Bitan Saha ◽  
Gloria Narayan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Delivery ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent ◽  
Insight Into

An Insight into DNA-free Reprogramming Approaches to Generate Integration-free Induced Pluripotent Stem Cells for Prospective Biomedical Applications

2018 ◽  
Vol 15 (2) ◽  
pp. 286-313 ◽  
Author(s):  
Manash P. Borgohain ◽  
Krishna Kumar Haridhasapavalan ◽  
Chandrima Dey ◽  
Poulomi Adhikari ◽  
Rajkumar P. Thummer
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Biomedical Applications ◽  
Induced Pluripotent ◽  
Insight Into
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