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

Project description: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

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RARγ is required for mesodermal gene expression prior to gastrulation

Project description:The developing vertebrate embryo is exquisitely sensitive to retinoic acid (RA) concentration, particularly during anteroposterior patterning. In contrast to Nodal and Wnt signaling, RA was not previously considered to be an instructive signal in mesoderm formation during gastrulation. Here we show that RARγ is indispensable for the expression of early mesoderm markers and is, therefore, an obligatory factor in mesodermal competence and/or maintenance. We identified several novel targets up-regulated by RAR signaling in the early gastrula that are expressed in the circumblastoporal ring and linked to mesodermal development. Despite overlapping expression patterns of the RA synthetic enzyme, Aldh1a2 and the RA- degrading enzyme, Cyp26a1, RARγ1 functions as a transcriptional activator in early mesoderm development, suggesting that RA ligand is available to the embryo earlier than previously appreciated. RARγ1 is required for cellular adhesion, as revealed by spontaneous dissociation and depletion of N-CAM mRNA in animal caps harvested from RARγ1 knockdown embryos. RARγ1 knockdown obliterates somite boundaries, and causes loss of MYOD protein in the presomitic mesoderm, but ectopic, persistent expression of MYOD protein in the trunk. Thus, RARγ1 is required for stabilizing the mesodermal fate, myogenic commitment, somite boundary formation, and terminal, skeletal muscle differentiation.

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Greb1 is required for axial elongation and segmentation in vertebrate embryos

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Self-Renewing Presomitic Mesoderm Progenitor Lines Reprogrammed from human urine cells [UiPSC and UiPSM scRNA-seq]

Project description:Self-Renewing Presomitic Mesoderm Progenitor Lines Reprogrammed from human urine cells [UiPSC and UiPSM scRNA-seq]

| PRJNA781940 | ENA

Transcription profiling of Xenopus laevis developing notochord

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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