EID1 knochdown by small RNA induces the large-scale conversion of adipose-derived mesenchymal stem cells into hematopoietic stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: James Yin
PROVIDER: E-GEOD-42650 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Comparison of expression profiles in adipose derived MSCs (AD-MSCs) without or with transfection of siR-EID1 and shR-EID1 and cord blood-derived HSCs (CB-HSCs). After MSCs were transfected with sRNA-EID1, they could be converted into HSCs. The goal was to determine possible molecular mechanisms of MSC transdetermination.
2012-12-01 | GSE42650 | GEO
Project description:Hepatic stellate cells (HSCs) experience phenotypic transformation, from the quiescent phenotype to the activated one, after different etiologies of liver injury. Liver fibrosis is then occurred upon the activation of HSCs. miR-16 deficiency is identified to be an important characteristic of HSCs activation. We used Affymetrix rat 230 2.0 arrays (Affymetrix, Santa Clara, U.S.A.) to uncover the global alternations of transcriptome under miR-16 restoration. We isolated quiescent hepatic stellate cells (HSCs) from adult male SD rats (normal control group) by in situ perfusion and density-gradient centrifugation. Activated HSCs were separated from rats of fibrosis model group, which were treated by 40% carbon tetrachloride (CCl4) for 8 weeks, by means of liver section, digestion and sequential centrifugation. Quiescent and activated HSCs were then divided into 4 groups at random, namely quiescent HSCs, activated HSCs, pLV-miR-16-treated HSCs and pLV-GFP-treated HSCs. The pLV-miR-16-treated group, pLV-GFP-treated group were infected with pLV-miR-16 and pLV-GFP, respectively.
2012-08-28 | E-GEOD-40381 | biostudies-arrayexpress
Project description:Myeloproliferative neoplasms (MPNs) are diseases caused by mutations in the haematopoietic stem cell (HSC) compartment. Most MPN patients have a common acquired mutation of Janus kinase 2 (JAK2) gene in HSCs that renders this kinase constitutively active, leading to uncontrolled cell expansion. The bone marrow (BM) microenvironment might contribute to the clinical outcomes of this common event. We previously showed that BM nestin+ mesenchymal stem cells (MSCs) innervated by sympathetic nerve fibres regulate normal HSCs. Here we demonstrate that abrogation of this regulatory circuit is essential for MPN pathogenesis. Sympathetic nerve fibres, supporting Schwann cells and nestin+ MSCs are consistently reduced in the BM of MPN patients and mice expressing the human JAK2V617F mutation in HSCs. Unexpectedly, MSC reduction is not due to differentiation but is caused by BM neural damage and Schwann cell death triggered by interleukin-1b produced by mutant HSCs. In turn, in vivo depletion of nestin+ cells or their production of CXCL12 expanded mutant HSCs and accelerated MPN progression. In contrast, administration of neuroprotective or sympathomimetic drugs prevented mutant HSC expansion. Treatment with b3-adrenergic agonists that restored the sympathetic regulation of nestin+ MSCs prevented the loss of these cells and blocked MPN progression by indirectly reducing leukaemic stem cells. Our results demonstrate that mutant HSC-driven niche damage critically contributes to disease manifestation in MPN and identify niche-forming MSCs and their neural regulation as promising therapeutic targets. Total RNA was isolated from BM CD45- CD31- Ter119- Nes-GFP+ cells obtained from Nes-gfp mice 10 weeks after transplantation with Mx1-cre;JAK2-V617F (n=3) or control cells (n=1). RNA was amplified using the NuGen Ovation system and hybridized to the Affymetrix MoGene 1.0 ST array.
2014-03-12 | E-GEOD-55801 | biostudies-arrayexpress
Project description:Human olfactory ecto-mesenchymal stem cells (hOE-MSCs) from controls and familial dysautonomia (FD) patients were cultured in either sphere-forming conditions (ITS + EGF + bFGF) or in the presence of retinoic acid, forskolin and Sonic Hedgehog (rafnshh) for 7 days to induce neuroglial differentiation and were also treated or not with kinetin (100 mM for 48h) which corrects the aberrant splicing of IKBKAP mRNA. We used the recently described model of human olfactory ecto-mesenchymal stem cells to identify genes differentially expressed between controls and familial dysautonomia patients, and also the genes sensitive to kinetin which corrects aberrant splicing of IKBKAP mRNA Total RNAs were extracted from 20 samples including: 4 control and 4 FD hOE-MSCs-derived sphere cultures, 4 control and 4 FD rafnshh-treated hOE-MSCs, 4 FD rafnshh-treated hOE-MSCs in the presence of kinetin
2012-01-01 | E-GEOD-27915 | biostudies-arrayexpress
Project description:The data presented is intended to analyse the changes in the expression profiles of human MSCs (Mesenchymal Stromal/Stem Cells) associated to different tissue specific stimulus. Human BM-, PL-, and AD- MSCs, and skin fibroblasts from healthy independent donors were isolated and expanded in vitro. Hematopoietic progenitors and stem cells (HSCs) were isolated applying CD34+ immunomagnetic selection.
2016-10-21 | E-GEOD-72332 | biostudies-arrayexpress
Project description:Exosomes transport biologically active cargo (e.g., proteins and microRNA) between cells, including many of the paracrine factors that mediate the beneficial effects associated with stem-cell therapy. Stem cell derived exosomes, in particular mesenchymal stem cells (MSCs), have been shown previously to largely replicate the therapeutic activity associated with the cells themselves, which suggests that exosomes may be a useful cell-free alternative for the treatment of cardiovascular disorders. However, the mechanisms that govern how exosomes home to damaged cells and tissues or the uptake and distribution of exosomal cargo are poorly characterized, because techniques for distinguishing between exosomal proteins and proteins in the targeted tissues are lacking. Here, we report the development of an in-vivo model that enabled the visualization, tracking, and quantification of proteins from systemically administered MSC exosomes. The model uses bioorthogonal chemistry and cell-selective metabolic labeling to incorporate the noncanonical amino acid azidonorleucine (ANL) into the MSC proteome. ANL incorporation is facilitated via expression of a mutant (L274G) methionyl-tRNA-synthetase (MetRS*) and subsequent incubation with ANL-supplemented media; after which ANL can be covalently linked to alkyne-conjugated reagents (e.g., dyes, resins) via click chemistry. Our results demonstrate that when the exosomes produced by ANL-treated, MetRS*-expressing MSCs were systemically administered to mice, the ANL-labeled exosomal proteins could be accurately and reliably identified, isolated, and quantified from a variety of mouse organs, and that myocardial infarction (MI) both increased the abundance of exosomal proteins and redistributed a number of them from the membrane fraction of intact hearts to the cytosol of cells in infarcted hearts. Additionally, we found that Desmoglein-1c is enriched in MSC exosomes and taken up by ischemic myocardium. Collectively, our results indicate that this newly developed bioorthogonal system can provide crucial insights into exosome homing, as well as the uptake and biodistribution of exosomal proteins.
2021-03-15 | PXD024485 | Pride
Project description:Exosomes transport biologically active cargo (e.g., proteins and microRNA) between cells, including many of the paracrine factors that mediate the beneficial effects associated with stem-cell therapy. Stem cell derived exosomes, in particular mesenchymal stem cells (MSCs), have been shown previously to largely replicate the therapeutic activity associated with the cells themselves, which suggests that exosomes may be a useful cell-free alternative for the treatment of cardiovascular disorders. However, the mechanisms that govern how exosomes home to damaged cells and tissues or the uptake and distribution of exosomal cargo are poorly characterized, because techniques for distinguishing between exosomal proteins and proteins in the targeted tissues are lacking. Here, we report the development of an in-vivo model that enabled the visualization, tracking, and quantification of proteins from systemically administered MSC exosomes. The model uses bioorthogonal chemistry and cell-selective metabolic labeling to incorporate the noncanonical amino acid azidonorleucine (ANL) into the MSC proteome. ANL incorporation is facilitated via expression of a mutant (L274G) methionyl-tRNA-synthetase (MetRS*) and subsequent incubation with ANL-supplemented media; after which ANL can be covalently linked to alkyne-conjugated reagents (e.g., dyes, resins) via click chemistry. Our results demonstrate that when the exosomes produced by ANL-treated, MetRS*-expressing MSCs were systemically administered to mice, the ANL-labeled exosomal proteins could be accurately and reliably identified, isolated, and quantified from a variety of mouse organs, and that myocardial infarction (MI) both increased the abundance of exosomal proteins and redistributed a number of them from the membrane fraction of intact hearts to the cytosol of cells in infarcted hearts. Additionally, we found that Desmoglein-1c is enriched in MSC exosomes and taken up by ischemic myocardium. Collectively, our results indicate that this newly developed bioorthogonal system can provide crucial insights into exosome homing, as well as the uptake and biodistribution of exosomal proteins.
2021-03-15 | PXD024483 | Pride
Project description:Exosomes transport biologically active cargo (e.g., proteins and microRNA) between cells, including many of the paracrine factors that mediate the beneficial effects associated with stem-cell therapy. Stem cell derived exosomes, in particular mesenchymal stem cells (MSCs), have been shown previously to largely replicate the therapeutic activity associated with the cells themselves, which suggests that exosomes may be a useful cell-free alternative for the treatment of cardiovascular disorders. However, the mechanisms that govern how exosomes home to damaged cells and tissues or the uptake and distribution of exosomal cargo are poorly characterized, because techniques for distinguishing between exosomal proteins and proteins in the targeted tissues are lacking. Here, we report the development of an in-vivo model that enabled the visualization, tracking, and quantification of proteins from systemically administered MSC exosomes. The model uses bioorthogonal chemistry and cell-selective metabolic labeling to incorporate the noncanonical amino acid azidonorleucine (ANL) into the MSC proteome. ANL incorporation is facilitated via expression of a mutant (L274G) methionyl-tRNA-synthetase (MetRS*) and subsequent incubation with ANL-supplemented media; after which ANL can be covalently linked to alkyne-conjugated reagents (e.g., dyes, resins) via click chemistry. Our results demonstrate that when the exosomes produced by ANL-treated, MetRS*-expressing MSCs were systemically administered to mice, the ANL-labeled exosomal proteins could be accurately and reliably identified, isolated, and quantified from a variety of mouse organs, and that myocardial infarction (MI) both increased the abundance of exosomal proteins and redistributed a number of them from the membrane fraction of intact hearts to the cytosol of cells in infarcted hearts. Additionally, we found that Desmoglein-1c is enriched in MSC exosomes and taken up by ischemic myocardium. Collectively, our results indicate that this newly developed bioorthogonal system can provide crucial insights into exosome homing, as well as the uptake and biodistribution of exosomal proteins.
2021-03-15 | PXD024484 | Pride
Project description:Exosomes transport biologically active cargo (e.g., proteins and microRNA) between cells, including many of the paracrine factors that mediate the beneficial effects associated with stem-cell therapy. Stem cell derived exosomes, in particular mesenchymal stem cells (MSCs), have been shown previously to largely replicate the therapeutic activity associated with the cells themselves, which suggests that exosomes may be a useful cell-free alternative for the treatment of cardiovascular disorders. However, the mechanisms that govern how exosomes home to damaged cells and tissues or the uptake and distribution of exosomal cargo are poorly characterized, because techniques for distinguishing between exosomal proteins and proteins in the targeted tissues are lacking. Here, we report the development of an in-vivo model that enabled the visualization, tracking, and quantification of proteins from systemically administered MSC exosomes. The model uses bioorthogonal chemistry and cell-selective metabolic labeling to incorporate the noncanonical amino acid azidonorleucine (ANL) into the MSC proteome. ANL incorporation is facilitated via expression of a mutant (L274G) methionyl-tRNA-synthetase (MetRS*) and subsequent incubation with ANL-supplemented media; after which ANL can be covalently linked to alkyne-conjugated reagents (e.g., dyes, resins) via click chemistry. Our results demonstrate that when the exosomes produced by ANL-treated, MetRS*-expressing MSCs were systemically administered to mice, the ANL-labeled exosomal proteins could be accurately and reliably identified, isolated, and quantified from a variety of mouse organs, and that myocardial infarction (MI) both increased the abundance of exosomal proteins and redistributed a number of them from the membrane fraction of intact hearts to the cytosol of cells in infarcted hearts. Additionally, we found that Desmoglein-1c is enriched in MSC exosomes and taken up by ischemic myocardium. Collectively, our results indicate that this newly developed bioorthogonal system can provide crucial insights into exosome homing, as well as the uptake and biodistribution of exosomal proteins.
2021-03-15 | PXD024482 | Pride
Project description:Analysis of human liver cell line (Huh7) infected with HEV ORF3 expressing (Ad-orf3-egfp) and control recombinant adenovirus (Ad-egfp). Hepatitis E virus ORF3 protein (pORF3) is known to modulate the host cell. Results provide insight into the role of this protein for HEV infection and pathogenesis. The gene expression experiment of Huh7 hepatoma cell line infected with ORF3 expressing recombinant adenoviruses (Ad-orf3-egfp) and with control recombinant adenoviruses (Ad-egfp) was performed in replicates of three.
2010-12-01 | E-GEOD-23412 | biostudies-arrayexpress