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Self-Renewing Presomitic Mesoderm Progenitor Lines Reprogrammed from human urine cells [Reprogramming ATAC-seq]

ABSTRACT: Vertebrae formation is the defining feature of all vertebrates1,2. Yet, each vertebrate species appears to have a unique timing mechanism for forming somites along the vertebral column3-5. Human vertebrate formation remains poorly studied due to technical and ethical limitations. Here we report the generation of self-renewing stem cells with characteristic presomitic mesoderm (PSM) features by reprogramming epithelial cells isolated from human urine. These induced expandable presomitic mesoderm progenitor cells (UiPSM) proliferated extensively for more than 30 passages in chemically defined conditions, robustly producing 1040 UiPSM cells. UiPSM established presomitic mesodermal transcription profile, not detected pluripotency, ectoderm and endoderm related genes. UiPSM developed into presomitic mesodermal lineage cells, such as skeletal muscle cells(skm), osteoblast and chrondroblast cells in vivo and vitro, when transplanted UiPSM derived human skm cells in muscle injury model, the skm cells can survive in vivo and contribute to muscle regeneration up to one month. Thus, UiPSM is a powerful system to study human somite development and provide strategies for regenerative medicine in musculoskeletal system

ORGANISM(S): Homo sapiens

PROVIDER: GSE186671 | GEO | 2024/07/26

REPOSITORIES: GEO

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Self-Renewing Presomitic Mesoderm Progenitor Lines Reprogrammed from human urine cells [Passage bulk RNA-seq]

Project description:Vertebrate formation is the defining feature of all vertebrates1,2. Yet, each vertebrate species appears to have a unique timing mechanism for forming somites along the vertebral column3-5. Human vertebrate formation remains poorly studied due to technical and ethical limitations. Here we report the generation of self-renewing stem cells with characteristic presomitic mesoderm (PSM) features by reprogramming epithelial cells isolated from human urine. These induced expandable presomitic mesoderm progenitor cells (UiPSM) proliferated extensively for more than 30 passages in chemically defined conditions, robustly producing 1040 UiPSM cells. UiPSM established presomitic mesodermal transcription profile, not detected pluripotency, ectoderm and endoderm related genes. UiPSM developed into presomitic mesodermal lineage cells, such as skeletal muscle cells(skm), osteoblast and chrondroblast cells in vivo and vitro, when transplanted UiPSM derived human skm cells in muscle injury model, the skm cells can survive in vivo and contribute to muscle regeneration up to one month. Thus, UiPSM is a powerful system to study human somite development and provide strategies for regenerative medicine in musculoskeletal system

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RARγ is required for mesodermal gene expression prior to gastrulation

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Project description:We screened for differentially expressed genes in the developing notochord using the Affymetrix microarray system in Xenopus laevis. At late gastrula, we dissected four regions from the embryo, anterior mesoderm, posterior mesoderm, notochord and presomitic mesoderm. Three types of comparison were carried out to generate a list of predominantly notochord expressed genes: (1) Posterior mesoderm vs. anterior mesoderm; notochord genes are expected to be increased since the notochord is located in the posterior mesoderm. (2) Posterior mesoderm vs. whole embryos; notochord genes are expected to be increased. (3) Notochord vs. somite. This comparison sub-divided the group of posterior mesodermal genes identified in (1) and (2). All tissues are dissected using tungsten needles. We first dissected dorsal tissue above the archenteron from late gastrula to early neurula. To loosen tissue, we treated the dissected dorsal explant in a 1% cysteine solution (pH 7.4) and removed the neuroectodermal layer. Anterior mesoderm was dissected corresponding to about the anterior one-third of the archenteron roof, and the rest was collected as posterior mesoderm. The posterior mesodermal explant was dissected into notochord and somites, following a clearly visible border between the two tissues. The accuracy of all dissection was confirmed by RT-PCR of marker genes.

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