Cardiopharyngeal Mesoderm specification into cardiac and skeletal muscle lineages in gastruloids
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ABSTRACT:
PROVIDER: PRJNA973944 | ENA |
REPOSITORIES: ENA
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Project description:Cardiopharyngeal mesoderm contributes to the formation of the heart and head muscles. However, the mechanisms governing cardiopharyngeal mesoderm specification remain unclear. Indeed, there is a lack of an in vitro model replicating the differentiation of both heart and head muscles to study these mechanisms. Such models are required to allow live-imaging and high throughput genetic and drug screening. Here, we show that the formation of self-organizing or pseudo-embryos from mouse embryonic stem cells (mESCs), also called gastruloids, reproduces cardiopharyngeal mesoderm specification towards cardiac and skeletal muscle lineages. By conducting a comprehensive temporal analysis of cardiopharyngeal mesoderm establishment and differentiation in gastruloids and comparing it to mouse embryos, we present the first evidence for skeletal myogenesis in gastruloids. By inferring lineage trajectories from the gastruloids single-cell transcriptomic data, we further suggest that heart and head muscles formed in gastruloids derive from cardiopharyngeal mesoderm progenitors. We identify different subpopulations of cardiomyocytes and skeletal muscles, which most likely correspond to different states of myogenesis with “head-like” and “trunk-like” skeletal myoblasts. These findings unveil the potential of mESC-derived gastruloids to undergo specification into both cardiac and skeletal muscle lineages, allowing the investigation of the mechanisms of cardiopharyngeal mesoderm differentiation in development and how this could be affected in congenital diseases.
2024-11-01 | GSE232773 | GEO
Project description:Patterning and growth are fundamental features of embryonic development that must be tightly coordinated during morphogenesis. While metabolism is known to control cell growth, how it impacts patterning and links to morphogenesis is poorly understood. To understand how metabolism impacts early mesoderm specification during gastrulation, we used in vitro mouse embryonic stem (ES) cell-derived gastruloids, due to ease of metabolic manipulations and high-throughput nature. Gastruloids showed mosaic expression of glucose transporters co-expressing with the mesodermal marker T/Bra. To understand the significance of cellular glucose uptake in development, we used the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG). 2-DG blocked the expression of T/Bra and abolishes axial elongation in gastruloids. Surprisingly, removing glucose completely from the medium did not phenocopy 2-DG treatment despite a significant decline in glycolytic intermediates occurring under both conditions. As 2-DG can also act as a competitive inhibitor of mannose in protein glycosylation, we added mannose together with 2-DG and found that it could rescue the mesoderm specification. We corroborated these results in vivomouse embryos where supplementing mannose rescued the 2-DG mediated phenotype of mesoderm specification and proximo-distal elongation of the primitive streak. We further showed that blocking production and intracellular recycling of mannose abrogated mesoderm specification. At molecular level, proteomics analysis revealed that mannose reversed glycosylation of the Wnt pathway regulator, Secreted Frizzled Receptor, Frzb, expressed in the primitive streak of the mouse embryo. Our study showed how mannose linked metabolism to glycosylation of a developmental pathway component, crucial in patterning of mesoderm and morphogenesis of gastruloids.
2024-01-12 | MSV000093849 | MassIVE
Project description:Patterning and growth are fundamental features of embryonic development that must be tightly coordinated during morphogenesis. As metabolism can control cell growth while also providing mechanistic links to developmental signalling pathways, it is ideally placed to enable this coordination. To understand how metabolism impacts early mesoderm specification, we used mouse embryonic stem (ES) cell-derived gastruloids, as these enable temporal control over metabolic manipulations and can be generated in large quantities. Gastruloids show mosaic expression of two glucose transporters,Slc2a1andSlc2a3both of which co-express with the expression of both the mesodermal markerT/Braand the neural markerSox2. To understand the significance of cellular glucose uptake in development, we used the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG). 2-DG specifically blocks the expression ofT/Brawithout affecting the expression ofSox2and abolishes axial elongation in gastruloids. Surprisingly, removing glucose completely from the medium did not phenocopy 2-DG treatment despite a significant decline in glycolytic intermediates occurring under both conditions. As 2-DG can also act as a competitive inhibitor of mannose, we added mannose together with 2-DG and found that it could rescue the mesoderm specification. Together, our results show that while mannose is crucial for mesoderm specification, the glycolytic pathway is dispensable at early stages ofT/Braexpression in gastruloids.
2024-03-11 | GSE236887 | GEO
Project description:In vertebrates, pluripotent pharyngeal mesoderm progenitors produce the cardiac precursors of the second heart field as well as the branchiomeric head muscles and associated stem cells. However, the cellular and molecular mechanisms underlying the transition from multipotent progenitors to distinct heart and muscle precursors remain obscured by the complexity of vertebrate embryos. Here, using the ascidian Ciona intestinalis as a simple chordate model for cardiopharyngeal development, we show that bipotent progenitors are transcriptionally primed to activate both heart and pharyngeal muscle regulatory programs, which become restricted to the corresponding precursors following a conserved pattern of asymmetric divisions. Localized expression of COE (Collier/OLF1/EBF) then orchestrates the transition to a pharyngeal muscle fate both by promoting an MRF (Myogenic Regulatory Factor)-associated core myogenic program in myoblasts and by maintaining an undifferentiated state in their sister precursors through Notch-mediated lateral inhibition. Using single cell lineage tracing, we show that the latter are stem-like muscle precursors, which form most of the juvenile body wall muscles following proliferation, self-renewal, re-activation of MRF, and migration. We discuss the implications of our findings for the development and evolution of the cardiopharyngeal mesoderm in chordates. We combined fluorescence-activated cell sorting (FACS) and whole genome transcription profiling following perturbations of COE function to characterize the transcriptional dynamics underlying the specification of heart and ASM precursors in the ascidian cardiopharyngeal lineage. We used whole genome transcription profiling of FACS-purified cell populations isolated from 21 hpf larvae expressing FoxF>COE, FoxF>COE::WRPW or the FoxF>NLS::lacZ control. To gain insights into the transcriptional dynamics underlying fate specification in the cardiopharyngeal lineage, we also purified B7.5-lineage cells from control embryos and larvae collected every two hours from 8 to 28 hpf. This time window encompasses all developmental transitions from early TVC specification till ASM ring formation and initial differentiation.
2014-07-17 | E-GEOD-54746 | biostudies-arrayexpress
Project description:Mannose is crucial for mesoderm specification and symmetry breaking in gastruloids
| PRJNA992567 | ENA
Project description:In the heart development, mesodermal progenitor cells in pharyngeal apparatus, termed cardiopharyngeal mesoderm, contribute to both atruim and right ventricle. Tbx1 gene, encoding a T-box transctiption factor and gene haploinsufficient in 22q11.2 deletion syndrome, is required for cardiac outflow tranct and branchiomeric muscle development. To understand how TBX1 affect open chromatin status in cardiopharyngeal mesoderm, we performed ATAC-seq in Tbx1-Cre lineage with/without Tbx1 expression.
2021-10-10 | GSE173700 | GEO
Project description:We have developed a protocol to generate cardiopharyngeal mesoderm (CPM) in vitro by Mesp1 induction in ES cells. The goal of this study is to compare the transcriptome of CPM-derived cardiac and skeletal myogenic progenitors to identify novel lineage-specific markers. mRNA profiles of CPM-derived D6 (early) and D12 (late), cardiac (BMP) and skeletal myogenic (control) progenitors were generated
2016-01-12 | E-GEOD-74682 | biostudies-arrayexpress
Project description:Mesoderm specification under hypoxia
| PRJNA721233 | ENA
Project description:We have developed a protocol to generate cardiopharyngeal mesoderm (CPM) in vitro by Mesp1 induction in ES cells. The goal of this study is to compare the transcriptome of CPM-derived cardiac and skeletal myogenic progenitors to identify novel lineage-specific markers.
2016-01-12 | GSE74682 | GEO
Project description:In vertebrates, pluripotent pharyngeal mesoderm progenitors produce the cardiac precursors of the second heart field as well as the branchiomeric head muscles and associated stem cells. However, the cellular and molecular mechanisms underlying the transition from multipotent progenitors to distinct heart and muscle precursors remain obscured by the complexity of vertebrate embryos. Here, using the ascidian Ciona intestinalis as a simple chordate model for cardiopharyngeal development, we show that bipotent progenitors are transcriptionally primed to activate both heart and pharyngeal muscle regulatory programs, which become restricted to the corresponding precursors following a conserved pattern of asymmetric divisions. Localized expression of COE (Collier/OLF1/EBF) then orchestrates the transition to a pharyngeal muscle fate both by promoting an MRF (Myogenic Regulatory Factor)-associated core myogenic program in myoblasts and by maintaining an undifferentiated state in their sister precursors through Notch-mediated lateral inhibition. Using single cell lineage tracing, we show that the latter are stem-like muscle precursors, which form most of the juvenile body wall muscles following proliferation, self-renewal, re-activation of MRF, and migration. We discuss the implications of our findings for the development and evolution of the cardiopharyngeal mesoderm in chordates. We combined fluorescence-activated cell sorting (FACS) and whole genome transcription profiling following perturbations of COE function to characterize the transcriptional dynamics underlying the specification of heart and ASM precursors in the ascidian cardiopharyngeal lineage.
2014-07-17 | GSE54746 | GEO