Single cell analysis of MNX1 overexpression in hemogenic gastruloids
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ABSTRACT:
PROVIDER: PRJEB56088 | ENA |
REPOSITORIES: ENA
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Project description:Analysis of MNX1 over expression in a 3-dimensional gastruloid differentiation system initiated from mouse embryonic stem (ES) cells and biased towards hemato-endothelial cell production.
2022-10-10 | E-MTAB-12149 | biostudies-arrayexpress
Project description:RNA sequencing of mouse embryonic stem cells (mES) and hemogenic gastruloids with MNX1 overexpression
| PRJEB75466 | ENA
Project description:Bulk RNA sequencing of 3-dimensional gastruloid differentiation system initiated from mouse embryonic stem (ES) cells and biased towards hemato-endothelial cell production with overexpression of MNX1 by lentiviral vector transduction
2022-10-10 | E-MTAB-12173 | biostudies-arrayexpress
Project description:Single cell transcriptomic study (using 10x Genomics v3 kits) of gastruloids, aggregates of mESCs, at different developmental timepoints (24h, 48h and 72h post-aggregation). mESCs, corresponding to the 0h timepoint, were also sequenced. The aim of this study was to delineate the cell state transition dynamics underlying anteroposterior symmetry breaking and germ layer formation in gastruloids. Gastruloids used in this study were generated from Bra::GFP reporter mESCs (Fehling et al., 2003).
2023-12-04 | E-MTAB-12749 | biostudies-arrayexpress
Project description:Gastruloids are three-dimensional aggregates of embryonic stem cells (ESCs) that display key features of mammalian post-implantation development, including germ layer specification and axial organization. Gastruloids have mostly been characterized with microscopy-based approaches, limiting the number of genes that can be explored. It is therefore unclear to what extent gene expression in gastruloids reflects in vivo embryonic expression. Using both single-cell RNA-seq (scRNA-seq) and spatial transcriptomics we systematically compared cell types and spatial expression patterns between mouse gastruloids and mouse embryos.
2019-12-05 | GSE123187 | GEO
Project description:Single cell analysis of gastruloid hemogenic development
| PRJEB56021 | ENA
Project description:Overexpression of transcription factor Sox17 in human ES cells-derived endothelial cells and hematopoietic cells enhances expansion of hemogenic endothelium-like cells.
2012-12-14 | GSE37348 | GEO
Project description:Motor neuron (MN), together with interneuron, are the two major neuronal types in spinal cord. MNs control muscle movement and are essential for breathing, walking and fine motor skills. Malfunction of MNs is frequently associated with neuronal diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis. To establish normal function, MNs need to be differentiated properly from neural progenitor cells. Thus, it is of great importance to study the mechanism for MN specification. This study focuses on Mnx1 - a conserved homeobox transcription factor gets expressed during MN specification. Mnx1 is also the most widely used MN marker. Previous studies reported that Mnx1 mutation in mouse causes early lethality - probably by affecting the controlling over respiratory system. However, the exact role of Mnx1 for MN identity remains poorly understood. Taking advantage of a recently developed in vitro model for efficient MN induction from mouse ES cells, we combined experimental and OMICs techniques to systematically investigate the molecular function of Mnx1. We identified thousands of Mnx1 binding sites - many are co-bound by core MN factor Lhx3 and Isl1 and lack active histone marks. Disruption of Mnx1 causes increased expression of 85 genes - while only 14 genes get down-regulated. Up-regulated genes are enriched with neuronal functions, usually get expressed during MN differentiation, and tend to have higher expression in motor neurons and brain compared with other tissues – indicating Mnx1 may fine tune neuronal genes to desired level. However, only a dozen of regions with increased H3K27ac marks are bound by Mnx1, and only two up-regulated genes (Pbx3 and Pou6f2) are identified as putative direct targets of Mnx1 - both are core neuronal factors with the potential to regulate other differential neuronal genes. These results suggest that Mnx1 may contribute to MN identity by fine-tuning the expression of many neuronal genes through direct regulation of a few core neuronal transcription factors. In summary, this study represents the first systematic investigation about the molecular function of the core MN factor Mnx1. It clarifies the mechanism of Mnx1 for MN identity, and also improves the understanding about the regulation mode of homeobox transcription factors.
2021-12-31 | GSE143161 | GEO
Project description:Gastruloids are a powerful in vitro model of early human development. However, although elongated and composed of all three germ layers, human gastruloids do not morphologically resemble post-implantation human embryos. Here we show that an early pulse of retinoic acid (RA), together with later Matrigel, robustly induces human gastruloids with posterior embryo-like morphological structures, including a neural tube flanked by segmented somites, and diverse cell types including neural crest, neural progenitors, renal progenitors, and myocytes. Through in silico staging based on single-cell RNA-seq (scRNA-seq), we find that human RA-gastruloids progress further than other human or mouse embryo models, aligning to E9.5 mouse and CS11 cynomolgus monkey embryos. We leverage chemical and genetic perturbations of RA-gastruloids to confirm that WNT and BMP signalling regulate somite formation and neural tube length in the human context, while transcription factors TBX6 and PAX3 underpin presomitic mesoderm and neural crest, respectively. Looking forward, RA-gastruloids are a robust, scalable model for decoding early human embryogenesis.
2024-06-20 | GSE208369 | GEO
Project description:Acute myeloid leukemia (AML) with translocation t(7;12)(q36;p13) is a subgroup that occurs only in infants or very young children and is characterised by a poor outcome. Deep molecular characterization has been hampered by the rarity of this AML subtype and the lack of model systems. Approximately 50% of AML with t(7;12)(q36;p13) express an MNX1::ETV6 oncofusion transcript, but there is no evidence for the presence of an oncofusion protein. However, a universal feature is the strong RNA and protein expression of MNX1, a homeobox transcription factor that is normally not transcribed in haematopoietic cells. Here we use whole genome sequencing data to precisely map the translocation breakpoints on chromosomes 7 and 12 in these pediatric AML patients to a region downstream of MNX1 on chromosome 7 and either introns 1 or 2 of ETV6 on chromosome 12. We confirm the tight correlation of MNX1 overexpression in t(7;12)(q36;p13) AML in our own samples and three additional cohorts of pediatric AML. Using a CRISPR-engineered iPSC cell line, ChiPSC22t(7;12), harbouring the t(7;12)(q36;p13) translocation, we unravel an enhancer-hijacking event leading to MNX1 overexpression. Identification of hematopoietic enhancer regions in hematopoietic stem and progenitor cells derived from differentiated ChiPSC22t(7;12) cells allowed us to demonstrate their importance for MNX1 expression in knock-out experiments and by measuring the promoter-enhancer distance in confocal microscopy. In contrast to the prevailing dogma in AML, suggesting that translocations lead to the creation of oncofusion genes, t(7;12)(q36;p13) AML is characterized by an enhancer-hijacking event driving MNX1, a novel leukemia oncogene and the haploinsufficiency of ETV6.
2024-08-21 | GSE244277 | GEO