The DiGeorge Syndrome gene TBX1 is required to specify the nkx2.5+ cardiopharyngeal lineage
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE103120 | GEO | 2018/07/31
REPOSITORIES: GEO
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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:Dynamic gene expression programs determine multipotent cell states and fate choices during development. Multipotent progenitors for cardiomyocytes and branchiomeric head muscles populate the pharyngeal mesoderm of vertebrate embryos, but the mechanisms underlying cardiopharyngeal multipotency and heart vs. head muscle fate choices remain elusive. The tunicate Ciona emerged as a simple chordate model to study cardiopharyngeal development with unprecedented spatio-temporal resolution. We analyzed the transcriptome of single cardiopharyngeal lineage cells isolated at successive time points encompassing the transitions from multipotent progenitors to distinct first and second heart, and pharyngeal muscle precursors. We reconstructed the three cardiopharyngeal developmental trajectories, and characterized gene expression dynamics and regulatory states underlying each fate choice. Experimental perturbations and bulk transcriptome analyses revealed that ongoing FGF/MAPK signaling maintains cardiopharyngeal multipotency and promotes the pharyngeal muscle fate, whereas signal termination permits the deployment of a full pan-cardiac program and heart fate specification. We identified the Dach1/2 homolog as a novel evolutionarily conserved second-heart-field-specific factor and demonstrate, through lineage tracing and CRISPR/Cas9 perturbations, that it operates downstream of Tbx1/10 to actively suppress the first heart lineage program. This data indicates that the regulatory state of multipotent cardiopharyngeal progenitors determines the first vs. second heart lineage choice, and that Tbx1/10 acts as a bona fide regulator of cardiopharyngeal multi potency. We performed bulk RNAseq to profile the FACS purified Ciona Robusta Truck Ventral Cells (TVCs) with FGF-MAPK perturbation conditions to address the question- What is the role of FGF signaling pathway during early cardiopharyngeal specification. we performed bulk RNA sequencing of FACS-purified cardiopharyngeal lineage cells isolated from embryos and larvae expressing either a dominant negative form the fibroblast growth factor receptor (dnFGFR), or a constitutively active form of M-Ras (caM-Ras), the sole Ras homolog in Ciona, under the control of TVC-specific enhancers.
2017-06-15 | GSE99845 | GEO
Project description:Dynamic gene expression programs determine multipotent cell states and fate choices during development. Multipotent progenitors for cardiomyocytes and branchiomeric head muscles populate the pharyngeal mesoderm of vertebrate embryos, but the mechanisms underlying cardiopharyngeal multipotency and heart vs. head muscle fate choices remain elusive. The tunicate Ciona emerged as a simple chordate model to study cardiopharyngeal development with unprecedented spatio-temporal resolution. We analyzed the transcriptome of single cardiopharyngeal lineage cells isolated at successive time points encompassing the transitions from multipotent progenitors to distinct first and second heart, and pharyngeal muscle precursors. We reconstructed the three cardiopharyngeal developmental trajectories, and characterized gene expression dynamics and regulatory states underlying each fate choice. Experimental perturbations and bulk transcriptome analyses revealed that ongoing FGF/MAPK signaling maintains cardiopharyngeal multipotency and promotes the pharyngeal muscle fate, whereas signal termination permits the deployment of a full pan-cardiac program and heart fate specification. We identified the Dach1/2 homolog as a novel evolutionarily conserved second-heart-field-specific factor and demonstrate, through lineage tracing and CRISPR/Cas9 perturbations, that it operates downstream of Tbx1/10 to actively suppress the first heart lineage program. This data indicates that the regulatory state of multipotent cardiopharyngeal progenitors determines the first vs. second heart lineage choice, and that Tbx1/10 acts as a bona fide regulator of cardiopharyngeal multi potency. 1823 FACS purified Ciona cardiopharyngeal progenitor cells at successive developmental stages (12, 14, 16, 18, 20 hpfs) have been sequenced in this research, encompassing the developmental spectrum from single multipotent progenitors to diverse fate-restricted progenitor cells. 1796 out of 1823 cells have reads successfully mapped to Ciona genome (i.e only 1796 samples have FPKM data in the *txt processed data files). We adopted multiple quality control criteria to filter out low quality single cell transcriptomes, the contaminating subpopulations and the doublets. Eventually, 848 high-quality cells were retained for further analysis. Based on previously identified cell type specific markers and the well established lineage tree, we identified all five cardiopharyngeal progenitor subtypes (TVC, STVC, ASM, FHP, SHP) and in silico reconstructed three unidirectional trajectories corresponding to the specification of pharyngeal and cardiac fate. Our study enabled us to characterize the global gene expression patterns of heterogeneous cardiopharyngeal progenitors, and interrogate the spatial-temporal dynamics of cardiopharyngeal specification.
2017-06-15 | GSE99844 | GEO
Project description:22q11 deletion syndrome (22q11DS) is mainly characterised by cardiovascular, craniofacial, thymic and parathyroid abnormalities. Haploinsufficiency of the transcription factor, TBX1 is considered to be a major underlying cause of these defects. Mice in which Tbx1 has been mutated phenocopy 22q11DS. In order to elucidate the transcriptional pathways regulated by Tbx1, the gene expression profile of Tbx1-lacZ positive cells isolated from E9.5 Df1/Tbx1lacZ embryos (Tbx1-null) were compared to cells isolated from Tbx1+/lacZ (Tbx1-heterozygous) embryos. This analysis has led to a better understanding of the pathways important in pharyngeal and heart development. Experiment design: 3 pools of cells (biological replicates) isolated from Df1/Tbx1lacZ embryos and Tbx1+/lacZ embryos were used for hybridisation onto 6 MOE430 v2 oligonucleotide array chips (Affymetrix), making 12 microarrays in total. Each pool of cells was isolated from at least 8 embryos.
2009-05-30 | E-MEXP-2096 | biostudies-arrayexpress
Project description:The heart and branchiomeric muscles are formed from the cardiopharyngeal mesoderm (CPM) during mammalian embryogenesis. The molecular mechanisms for lineage progression in the CPM in mammals remain elusive. Here, we have used single cell RNA-seq and lineage analysis and identified a cardiopharyngeal niche containing multilineage primed cells termed multilineage progenitors (MLPs), which is maintained throughout maturation of the pharyngeal apparatus. We found that MLP function is dependent on Tbx1, encoding a T-box transcription factor and the gene for 22q11.2 deletion syndrome. TBX1 positively regulates novel MLP enriched genes such as Aplnr and Nrg1, as well as known CPM genes related to both BrM and cardiac muscle cell development. Further, loss of Tbx1 results in ectopic expression of neuronal and other non-mesodermal specification genes such as Bdnf and Pax8, respectively, indicating that normal developmental regulation is disrupted. Integration of the multi-omic data generated a TBX1 gene regulatory network, including Isl1, Pitx2, Foxc2, Six1/2 and Tcf21, that regulates CPM lineage progression from MLPs. Our finding suggests that TBX1 is a one of the key regulators in MLP to maintain CPM property and promote differentiation toward both BrM and cardiac muscle cells.
2021-10-10 | GSE168768 | GEO
Project description:The heart and branchiomeric muscles are formed from the cardiopharyngeal mesoderm (CPM) during mammalian embryogenesis. The molecular mechanisms for lineage progression in the CPM in mammals remain elusive. Here, we have used single cell RNA-seq and lineage analysis and identified a cardiopharyngeal niche containing multilineage primed cells termed multilineage progenitors (MLPs), which is maintained throughout maturation of the pharyngeal apparatus. We found that MLP function is dependent on Tbx1, encoding a T-box transcription factor and the gene for 22q11.2 deletion syndrome. TBX1 positively regulates novel MLP enriched genes such as Aplnr and Nrg1, as well as known CPM genes related to both BrM and cardiac muscle cell development. Further, loss of Tbx1 results in ectopic expression of neuronal and other non-mesodermal specification genes such as Bdnf and Pax8, respectively, indicating that normal developmental regulation is disrupted. Integration of the multi-omic data generated a TBX1 gene regulatory network, including Isl1, Pitx2, Foxc2, Six1/2 and Tcf21, that regulates CPM lineage progression from MLPs. Our finding suggests that TBX1 is a one of the key regulators in MLP to maintain CPM property and promote differentiation toward both BrM and cardiac muscle cells.
2021-10-10 | GSE167491 | GEO
Project description:The heart and branchiomeric muscles are formed from the cardiopharyngeal mesoderm (CPM) during mammalian embryogenesis. The molecular mechanisms for lineage progression in the CPM in mammals remain elusive. Here, we have used single cell RNA-seq and lineage analysis and identified a cardiopharyngeal niche containing multilineage primed cells termed multilineage progenitors (MLPs), which is maintained throughout maturation of the pharyngeal apparatus. We found that MLP function is dependent on Tbx1, encoding a T-box transcription factor and the gene for 22q11.2 deletion syndrome. TBX1 positively regulates novel MLP enriched genes such as Aplnr and Nrg1, as well as known CPM genes related to both BrM and cardiac muscle cell development. Further, loss of Tbx1 results in ectopic expression of neuronal and other non-mesodermal specification genes such as Bdnf and Pax8, respectively, indicating that normal developmental regulation is disrupted. Integration of the multi-omic data generated a TBX1 gene regulatory network, including Isl1, Pitx2, Foxc2, Six1/2 and Tcf21, that regulates CPM lineage progression from MLPs. Our finding suggests that TBX1 is a one of the key regulators in MLP to maintain CPM property and promote differentiation toward both BrM and cardiac muscle cells.
2021-10-10 | GSE158941 | GEO
Project description:The heart and branchiomeric muscles are formed from the cardiopharyngeal mesoderm (CPM) during mammalian embryogenesis. The molecular mechanisms for lineage progression in the CPM in mammals remain elusive. Here, we have used single cell RNA-seq and lineage analysis and identified a cardiopharyngeal niche containing multilineage primed cells termed multilineage progenitors (MLPs), which is maintained throughout maturation of the pharyngeal apparatus. We found that MLP function is dependent on Tbx1, encoding a T-box transcription factor and the gene for 22q11.2 deletion syndrome. TBX1 positively regulates novel MLP enriched genes such as Aplnr and Nrg1, as well as known CPM genes related to both BrM and cardiac muscle cell development. Further, loss of Tbx1 results in ectopic expression of neuronal and other non-mesodermal specification genes such as Bdnf and Pax8, respectively, indicating that normal developmental regulation is disrupted. Integration of the multi-omic data generated a TBX1 gene regulatory network, including Isl1, Pitx2, Foxc2, Six1/2 and Tcf21, that regulates CPM lineage progression from MLPs. Our finding suggests that TBX1 is a one of the key regulators in MLP to maintain CPM property and promote differentiation toward both BrM and cardiac muscle cells.
2021-11-01 | GSE186934 | 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:The transcription factor Nkx2.5 is required for specification of pharyngeal arch second heart field (SHF) progenitors that contribute to outflow tract (OFT) and right ventricle (RV) formation. Multiple sets of microarray data were analyzed to identify genes that are candidate targets of Nkx2.5 in the second heart field. These sets are: 1) publicly available data for cardiothoracic tissue from E9.5 Nkx2.5 wild-type, heterozygous and homozygous embryos; 2) an analysis of mouse E10.5 pharyngeal arch tissue; 3) an analysis of mouse E12.5 heart tissue; and 4) a temporal analysis of the cardiogenic cell line P19CL6. This combined analysis identified 11 genes (Lrrn1, Elovl2, Safb, Slc39a6, Khdrbs1, Hoxb4, Fez1, Ccdc117, Jarid2, Nrcam, and Enpp3) expressed in SHF-containing pharyngeal arch tissue whose regulation is dependent on Nkx2.5 expression. Refer to individual Series
2010-05-17 | E-GEOD-17936 | biostudies-arrayexpress