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Characterization and therapeautic application of mesenchymal stem cells with neuromesodermal origin from human pluripotent stem cells

ABSTRACT: Characterization and therapeautic application of mesenchymal stem cells with neuromesodermal origin from human pluripotent stem cells

PROVIDER: PRJNA493024 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7899190_1.fastq.gz	Fastqsanger.gz
	SRR7899190_2.fastq.gz	Fastqsanger.gz
	SRR7899191_1.fastq.gz	Fastqsanger.gz
	SRR7899191_2.fastq.gz	Fastqsanger.gz
	SRR7899192_1.fastq.gz	Fastqsanger.gz

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Characterization and therapeautic application of mesenchymal stem cells with neuromesodermal origin from human pluripotent stem cells

Project description:Here, human pluripotent stem cells (including hiPSC and hESC) were induced to differentiate to mesenchymal stem cells (MSC) through the intermediate stage of neuromesoderm (NMP). We sequenced mRNA samples at different stages during NMP-MSC differentiation of human pluripotent stem cells to generate the gene expression profiles of these cells.

2019-05-17 | GSE120420 | GEO

Characterization and Therapeutic Application of Mesenchymal Stem Cells with Neuromesodermal Origin from Human Pluripotent Stem Cells.

Project description:Rationale: Mesenchymal stem cells (MSC) hold great promise in the treatment of various diseases including autoimmune diseases, inflammatory diseases, etc., due to their pleiotropic properties. However, largely incongruent data were obtained from different MSC-based clinical trials, which may be partially due to functional heterogeneity among MSC. Here, we attempt to derive homogeneous mesenchymal stem cells with neuromesodermal origin from human pluripotent stem cells (hPSC) and evaluate their functional properties. Methods: Growth factors and/or small molecules were used for the differentiation of human pluripotent stem cells (hPSC) into neuromesodermal progenitors (NMP), which were then cultured in animal component-free and serum-free induction medium for the derivation and long-term expansion of MSC. The resulted NMP-MSC were detailed characterized by analyzing their surface marker expression, proliferation, migration, multipotency, immunomodulatory activity and global gene expression profile. Moreover, the in vivo therapeutic potential of NMP-MSC was detected in a mouse model of contact hypersensitivity (CHS). Results: We demonstrate that NMP-MSC express posterior HOX genes and exhibit characteristics similar to those of bone marrow MSC (BMSC), and NMP-MSC derived from different hPSC lines show high level of similarity in global gene expression profiles. More importantly, NMP-MSC display much stronger immunomodulatory activity than BMSC in vitro and in vivo, as revealed by decreased inflammatory cell infiltration and diminished production of pro-inflammatory cytokines in inflamed tissue of CHS models. Conclusion: Our results identify NMP as a new source of MSC and suggest that functional and homogeneous NMP-MSC could serve as a candidate for MSC-based therapies.

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Project description:mouse embryonic fibroblasts, embryonic stem cells, and induced pluripotent stem cells were compared via metabolomic analysis

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Transcriptomic profiling of human neuromesodermal-like cells and spinal cord progenitors derived in vitro from H9 ES cell line

Project description:Human ES (H9) cells were directed towards a neuromesodermal progenitor-like cell state and these cells were then subsequently differentiated towards a neural cell fate. Human ES cells (H9) were differentiated into neuromesodermal progenitor-like cells by culturing in Neurobasal/1x N2/1x B27 medium (N2/B27) supplemented with 20 ng/ml bFgf and 3 μM CHIR99021 for 3 days and exposure to dual SMAD inhibition (dSMADi) (Noggin 50 ng/ml and the TGFb receptor type 1 inhibitor SB431542 10 μM) during day 3 (D3). Transcriptome analysis was then carried out following a selection procedure to enrich for NMP-like cells (sD3/NMP-like). This involved use of a hES (H9) cell line engineered with CRISPR-Cas9 to express GFP under the control of the endogenous Nkx1.2 promoter. At the end of day 3 cells were selected for high GFP expression, as high Nkx1.2 transcription is characteristic of NMP cell populations in mouse and chick embryos. These cells were then lysed and RNA extracted for RNASeq. Humans ES cells (H9) differentiated into NMP-like cells as above (without selection) were also allowed to develop further on day 4 (in the presence of dSMADi and Retinoic acid (RA) 100nM, in N2/B27) and then in RA alone until end of day 8 (D8). These cells were then lysed and RNA extracted for RNASeq.

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Project description:Colorectal cancer is a common disease worldwide. Increasing evidence is demonstrating that colorectal cancers arise from ‘cancer stem cells.’ Stem cells in the colon reside at the bottom of thousands of microscopic crypts throughout the wall of the colon. They create all the cells lining the bowel wall. These cells are created in the base of the crypt and ascend to the top acquiring the characteristics of mature cells of the bowel wall as they ascend. It is now thought that colorectal cancer cells arise from stem cells where the genetic material regulating growth and division of the stem cell has become defective. This leads to unregulated production of cells which in turn have defective genetic information and cancer formation. Prior studies have demonstrated that the earliest changes before a cancer develops are changes in cellular proliferation. Now that reliable markers to identify stem cells have been found, the researchers aim to investigate stem cell numbers and changes in distribution in those at normal risk of colorectal cancer and those at higher risk. The researchers hypothesise that changes in cellular proliferation at the top of the crypt in individuals at higher risk of colorectal cancer are due to a change in the number of stem cells in the crypt base.

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