Defining the skeletal myogenic lineage in human pluripotent stem cell-derived teratomas
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PROVIDER: PRJNA785485 | ENA |
REPOSITORIES: ENA
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Project description:Skeletal muscle stem cells are essential to muscle homeostasis and regeneration after injury. An attractive approach to obtain these cells is via differentiation of pluripotent stem cells (PSCs). We have recently reported that teratomas derived from mouse PSCs are a rich source of skeletal muscle stem cells. Here, we showed that the teratoma formation method is also capable of producing skeletal myogenic progenitors from human PSCs. Using single-cell transcriptomics, we discovered multiple lineages in human PSC-derived teratomas. Interestingly, we observed several distinct skeletal myogenic subpopulations. Trajectory analysis revealed that these subpopulations represented progressive stages of skeletal myogenic development. We further discovered that ERBB3 and CD82 are effective surface markers for prospective isolation of the skeletal myogenic lineage in human PSC-derived teratomas. Therefore, teratoma formation provides an accessible model for obtaining human skeletal myogenic progenitors from PSCs.
2022-05-18 | GSE189985 | GEO
Project description:The developmental trajectory of human skeletal myogenesis and the transition between progenitor and stem cell states are unclear. To address this, we employed single cell RNA-sequencing to profile human skeletal muscle tissues from embryonic, fetal and postnatal stages. In silico, we identified myogenic as well as other cell types and constructed a “roadmap” of human skeletal muscle ontogeny across development. In a similar fashion, we also profiled the heterogeneous cell cultures generated from multiple human pluripotent stem cell (hPSC) myogenic differentiation protocols, and mapped hPSC-derived myogenic progenitors to an embryonic-to-fetal transition period. Additionally, we found differentially enriched biological processes and discovered co-regulated gene networks and transcription factors present at distinct myogenic stages. In summary, this work serves as a resource for advancing our knowledge of human myogenesis. It also provides a tool for better characterization and understanding of hPSC-derived myogenic progenitors for translational applications in skeletal muscle based regenerative medicine.
2020-04-29 | GSE147457 | GEO
Project description:This work examines sarcoma formation within discrete subsets of KRAS(G12V)-expressing p16p19null myogenic and mesenchymal cells found normally in skeletal muscle. We show that prospectively isolated skeletal muscle precursor cells (SMPs) within the satellite cell pool can serve as cancer cells-of-origin for mouse rhabdomyosarcomas (soft tissue sarcomas with features of myogenic differentiation). Alternatively, non-myogenic progenitors (ScaPCs) induce sarcomas lacking myogenic differentiation markers. We used Affymetrix whole mouse genome 430 2.0 microarrays to gain deeper insights into the molecular underpinnings of the three types of KRAS; p16p19null mouse soft-tissue sarcomas (originating from SMPs, ScaPCs and CD45-MAC1-TER119-Sca1-CXCR4- cells). Four replicates of each type.
2011-11-10 | E-GEOD-22841 | biostudies-arrayexpress
Project description:Zinc finger E-box-binding homeobox 2 (ZEB2, also known as SMAD interacting protein 1 or Zfhx1b) protein is a transcription factor involved in the transforming growth factor β (TGFβ) and bone morphogenetic proteins (BMPs) signaling pathways. ZEB2 is a two-handed zinc-finger closely related to ZEB1 (ZFHX1a/δEF1) and it is present in many tissues including cardiac and skeletal muscles. Skeletal muscle development and adult myogenesis are regulated by helix-loop-helix proteins, including MyoD, Myf5, myogenin and MRF-4. It has been shown that ZEB1 (ZFHX1a/δEF1) competes with the myogenic regulatory factors for their consensus sequences on some target genes during muscle differentiation, however the role of ZEB2 in myogenesis is still unknown. In the present study, we evaluated the myogenic potential of Zeb2-null and R26_Zeb2 mouse embryonic stem cells by single-cell RNA-sequencing and tested muscle engraftment capability of the respective myogenic progenitors. Our results support the implication of Zeb2 in promoting myogenesis in pluripotent stem cells and myogenic progenitors by modulating specific genes encoding components of the TGFβ/BMP signaling system.
2020-03-31 | GSE147744 | GEO
Project description:This work examines sarcoma formation within discrete subsets of KRAS(G12V)-expressing p16p19null myogenic and mesenchymal cells found normally in skeletal muscle. We show that prospectively isolated skeletal muscle precursor cells (SMPs) within the satellite cell pool can serve as cancer cells-of-origin for mouse rhabdomyosarcomas (soft tissue sarcomas with features of myogenic differentiation). Alternatively, non-myogenic progenitors (ScaPCs) induce sarcomas lacking myogenic differentiation markers.
2011-11-10 | GSE22841 | GEO
Project description:Human pluripotent stem cells (hPSCs) tend to acquire genomic aberrations in culture, the most common of which is the trisomy of chromosome 12. Interestingly, trisomy 12 is also prevalent in germ cell tumors (GCTs). Here, we aimed to dissect the cellular and molecular implications of trisomy 12 in hPSCs. A genome-wide gene expression analysis revealed that trisomy 12 profoundly affects the global gene expression profile of hPSCs, inducing a transcriptional program very similar to that of CGTs. Direct comparison of the proliferation, replication, differentiation and apoptosis between diploid and aneuploid hPSCs revealed that trisomy 12 significantly increases the proliferation rate of hPSCs. Increased replication largely accounts for the increased proliferation observed, and may explain the selection advantage that trisomy 12 confers to hPSCs. A comparison of the tumors induced by diploid and aneuploid hPSCs further demonstrated that trisomy 12 increases the tumorigenicity of hPSCs, inducing transcriptionally-distinct teratomas, from which pluripotent cells can be recovered. Lastly, a chemical screen of 89 anticancer drugs against diploid and aneuploid hPSCs discovered that trisomy 12 raises the sensitivity of hPSCs to several replication inhibitors, suggesting that the increased proliferation and tumorigenicity of these aberrant cells also makes them more vulnerable, and might potentially be used for their selective elimination from culture. Together, our findings demonstrate the extensive effect of trisomy 12 on the gene expression signature and on the cellular behavior of hPSCs, and highlight the danger posed by this trisomy for the successful use of hPSCs in basic research and in regenerative medicine. Expression data from diploid and aneuoploid human pluripotent stem cells, teratomas derived from them, and pluripotent-like cells recovered from these teratomas total RNA was isolated from undifferentiated human pluripotent stem cells grown under standard human ES conditions, or from teratomas derived from them, or from ES-like cells recovered from these teratomas.
2014-09-01 | E-GEOD-51455 | biostudies-arrayexpress
Project description:Analysis of the transcriptome of zebrafish mononuclear myogenic cells (zMNCs) during myogenic differentiation. The main goal is to identify the similarities of zMNC myogenic differentiation with that of mammalian myoblast differentiation. Critical time points were used to identify a switch from the activity of cell proliferation genes to myogenic structural genes. 15-20 adult zebrafish dorsal skeletal muscles were isolated at each of 6 distinct time points (day 0, day 1, day 4, day 7, day 10, day 14) in replicates.
2010-04-07 | E-GEOD-19754 | biostudies-arrayexpress
Project description:Skeletal muscle is a highly organized and regenerative tissue that maintains its homeostasis primarily by activation and differentiation of muscle stem cells. Mimicking an in vitro skeletal muscle differentiation program that contains self-renewing adult muscle stem cells and aligned myotubes has been challenging. Here, we set out to engineer a biomimetic skeletal muscle construct that can self-regenerate and produce aligned myotubes using induced myogenic progenitor cells (iMPCs), a heterogeneous culture consisting of skeletal muscle stem, progenitor and differentiated cells. Utilizing electrospinning, we fabricated polycaprolactone (PCL) substrates that enabled iMPC-differentiation into aligned myotubes by controlling PCL fiber orientation. Newly-conceived constructs contained highly organized multinucleated myotubes in conjunction with self-renewing muscle stem cells, whose differentiation capacity was augmented by Matrigel supplementation. Additionally, we demonstrate using single cell RNA sequencing (scRNA-seq) that iMPC-derived constructs faithfully recapitulate a step-wise myogenic differentiation program. Notably, when the constructs were subjected to a damaging myonecrotic agent, self-renewing muscle stem cells rapidly differentiated into aligned myotubes, akin to skeletal muscle repair in vivo. Taken together, we report on a novel in vitro system that mirrors myogenic regeneration and muscle fiber alignment, and can serve as a platform to study myogenesis, model muscular dystrophies or perform drug screens.
2023-09-27 | GSE222162 | GEO
Project description:We generated the human ES lines, in which the genome-wide reduction of H3K27me3 can be induced by the ectopic expression of catalytic domain of histone demethylase JMJD3 with doxycycline treatment (JMJD3c-hESCs). The overexpression of JMJD3c enhances MYOD1-mediated myogenic differentiation of hESCs. We compared the gene expression patterns of the generated myogenic cells with those of human skeletal myotubes.
2016-10-18 | GSE80106 | GEO
Project description:Teratoma formation is the gold standard assay for testing the capacity of human stem cells to differentiate into all embryonic germ layers. Although widely used, little effort has been made to transform this qualitative assay into a quantitative one. Using gene expression data from a wide variety of cells, we created a gene scorecard representing tissues from all three germ layers as well as an extraembryonic tissue. A calculated grade using this gene list successfully distinguishes pluripotent stem cell-initiated teratomas from malignant tumors, thereby translating cell potency into a quantitative measure. This new methodology, named TeratoScore, thus assesses the pluripotency of human cells, and is easily performed using an open-source code. The new teratoma database also allowed us to examine the gene expression differences between tumors with a diploid karyotype and those initiated by aneuploid cells. We found that while teratomas originating from aneuploid cells pass the TeratoScore benchmark for pluripotency, they exhibit aberrant gene expression congruent with human chromosomal syndromes (such as Down syndrome). This gene expression signature is significantly different from that of teratomas originating from diploid cells, particularly in central nervous system-specific genes, suggesting aberrant teratomas may be beneficial for in vivo disease modeling. Teratoma formation followed by TeratoScore analysis can rapidly assess cell potency and allows comparison between different pluripotent cell lines. Total RNA was extracted from hPSC (diploid or aneuploid)-derived teratomas using RNeasy mini kit (Qiagen), according to the manufacture instruction. RNA was subjected to Human Genome U133 Plus 2.0 microarray platform (Affymetrix); washing and scanning were performed according to the manufacturer’s protocol
2015-06-10 | E-GEOD-64669 | biostudies-arrayexpress