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Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation [scRNA-seq]

ABSTRACT: Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation [scRNA-seq]

PROVIDER: PRJNA1070267 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27755777.fastq.gz	Fastqsanger.gz
	SRR27755778.fastq.gz	Fastqsanger.gz

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Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation

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Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation [RNA-seq]

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Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation [scRNA-seq]

Project description:Satellite cells, the stem cells of skeletal muscle tissue, hold a remarkable regeneration capacity and therapeutic potential in regenerative medicine. However, low satellite cell yield from autologous or donor-derived muscles hinders the adoption of satellite cell transplantation for the treatment of muscle diseases, including Duchenne muscular dystrophy (DMD). To address this limitation, here we investigated whether satellite cells can be derived in allogeneic or xenogeneic animal hosts. First, injection of CRISPR/Cas9-corrected mouse DMD-induced pluripotent stem cells (iPSCs) into mouse blastocysts carrying an ablation system of host satellite cells gave rise to intraspecies chimeras exclusively carrying iPSC-derived satellite cells. Furthermore, injection of genetically corrected DMD-iPSCs into rat blastocysts resulted in the formation of interspecies rat-mouse chimeras harboring mouse satellite cells. Remarkably, iPSC-derived satellite cells or derivative myoblasts produced in intraspecies or interspecies chimeras restored dystrophin expression in DMD mice following intramuscular transplantation, and contributed to the satellite cell pool. Collectively, this study demonstrates the feasibility of producing therapeutically competent stem cells across divergent animal species, raising the possibility of generating human muscle stem cells in large animals for regenerative medicine purposes.

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Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation [RNA-seq]

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Project description:This SuperSeries is composed of the SubSeries listed below.

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Xenogeneic Skin Transplantation Promotes Angiogenesis and Tissue Regeneration

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Induction of Local Immunosuppression in Allogenic Cell Transplantation by Cell-type-specific Expression of PD-L1 and CTLA4Ig

Project description:Immune rejection has long hindered allogenic cell transplantation therapy. Current genetic modification approaches, including direct targeting of major histocompatibility complex or constitutive expression of immune inhibitory molecules, exhibit drawbacks such as severe adverse effects or an elevated risk of tumorigenesis. To overcome these limitations, we propose an innovative approach aimed at inducing cell-type-specific immune tolerance in differentiated cells. By engineering human embryonic stem cells, we enable the exclusive production of immune inhibitory molecules, PD-L1/CTLA4Ig, within differentiated cells following lineage commitment. Leveraging this approach, we have successfully generated hepatocyte-like cells expressing PD-L1 and CTLA4Ig, which effectively induced local immunotolerance. This strategy was evaluated in a humanized mouse model designed to mimic human immune system. Our results demonstrate robust and selective induction of immunotolerance specific to hepatocytes, thereby improving graft survival without tumor formation. This precise immune tolerance strategy holds promise for advancing the development of stem cell-based therapeutics in regenerative medicine.

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Induction of Local Immunosuppression in Allogenic Cell Transplantation by Cell-type-specific Expression of PD-L1 and CTLA4Ig

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Intramuscular fat variability in pigs

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