Similar Datasets
Project description:HOXA13 Cut & Run of Human Melanoma Cells
| PRJNA753322 | ENA
Project description:SALL4 builds a complex with histone deacetylases, and is thought to confer its effects epigenetically. Both loss of Sall4 and inhibition of HDAC2 leads to an invasiveness in human melanoma cells. To study co-occupancy of SALL4 and HDAC2, we employed CUT&RUN targeting SALL4 and HDAC2 in human melanoma cells (M010817).
2021-06-30 | E-MTAB-10163 | biostudies-arrayexpress
Project description:CUT&RUN LoV-U was performed against SMAD4 using two different antibodies in M170117 human melanoma cells under 4 conditions: Control (DMSO), TGFb, MEKi and TGFb + MEKi (Both).
2024-04-22 | E-MTAB-13951 | biostudies-arrayexpress
Project description:The salamander limb regenerates only the missing portion. Each limb segment can only form segments equivalent to- or more distal to their own identity, relying on a property termed “positional information”. How positional information is encoded in limb cells has been unknown. By cell-type-specific chromatin profiling of upper arm, lower arm, and hand, we found segment-specific levels of histone H3K27me3 at limb homeoprotein gene loci but not their upstream regulators, constituting an intrinsic segment information code. During regeneration, regeneration-specific regulatory elements became active prior to the re-appearance of developmental regulatory elements. This means that, in the hand segment, the permissive chromatin state of the hand homeoprotein gene HoxA13 engages with regeneration regulatory elements, bypassing the upper limb program. Profiling histone marks of Axoltol limb connective tissue cells, and comparing among limb different limb segments and mature vs regeneration time points.
2023-04-10 | GSE217591 | GEO
Project description:Oncogenic alterations to DNA are not transforming in all cellular contexts. This may be due to pre-existing transcriptional programs in the cell of origin. Here, we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet, or under the nails. We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma but CRKL amplifications in acral melanoma. We modeled these changes in transgenic zebrafish models and found that CRKL-driven tumors predominantly formed in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin/limb melanocytes, compared to body melanocytes, revealed a positional identity gene program typified by posterior HOX13 genes. This positional gene program synergized with CRKL to drive tumors at acral sites. Abrogation of this CRKL-driven program eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults.
2022-01-12 | PXD027968 | Pride
Project description:Background and aims: Class I Homeobox (HOX) genes are fundamental components of embryonic patterning and morphogenesis, also implicated in neoplastic transformations. Among them HOXA13, in particular, has been found to be the most overexpressed in HCC and to be associated with worse prognosis. However, no previous work has shown so far a direct causal effect between HOXA13 overexpression and liver tumorigenesis. In this study we aimed to prove the direct oncogenicity of HOXA13 in the liver and to unravel the molecular mechanisms of Hoxa13-induced liver tumorigenesis. Approach and Results: To unravel the oncogenic mechanism of HOXA13 in vivo, a transgenic mouse model of HOXA13 overexpression in the liver was generated using hydrodynamic tail vein injection coupled with a transposase system. The mice phenotype was followed over time, from 2 weeks up to 1-year post injection. RNA-sequencing was performed to monitor the transcriptomic changes over time. HOXA13-overexpression in the liver led to highly proliferative hepatocytes and correlated with the DNA damage marker yH2AX. 1-year post-injection 50% of the injected mice developed liver tumors of various histological grades and types. RNA-sequencing analysis performed on whole liver extracts of 2 weeks-old mice and tumors showed that the main pathway deregulated by HOXA13 overexpression was cell cycle, in particular G2/M transition and mitotic spindle assembly checkpoint. Additionally, HOXA13-overexpressing livers showed a transcriptomic signature of chromosomal Instability, suggesting a possible mechanism of tumorigenesis driven by genome instability. Conclusions: Our study highlights the role of HOXA13 as a novel oncogenic driver in hepatocarcinogenesis and strongly suggests that its oncogenic properties are least partially mediated by induction of chromosomal instability.
2021-02-09 | GSE166341 | GEO
Project description:Barrett’s esophagus in gastrointestinal reflux patients constitutes a columnar epithelium with distal characteristics, prone to progress to esophageal adenocarcinoma. HOX genes are known mediators of position-dependent morphology. Here we show HOX collinearity in the adult gut while Barrett’s esophagus shows high HOXA13 expression in stem cells and their progeny. HOXA13 overexpression appears sufficient to explain both the phenotype (through downregulation of the epidermal differentiation complex) and the oncogenic potential of Barrett’s esophagus. Intriguingly, employing a mouse model that contains a reporter coupled to the HOXA13 promotor we identify single HOXA13-positive cells distally from the physiological esophagus, which is mirrored in human physiology, but increased in BE. Additionally, we observe that HOXA13 expression confers a competitive advantage to cells. We thus propose that Barrett’s esophagus and associated esophageal adenocarcinoma is the consequence of expansion of this gastro-esophageal HOXA13-expressing compartment following epithelial injury.
2021-04-24 | GSE173169 | GEO
Project description:Barrett’s esophagus in gastrointestinal reflux patients constitutes a columnar epithelium with distal characteristics, prone to progress to esophageal adenocarcinoma. HOX genes are known mediators of position-dependent morphology. Here we show HOX collinearity in the adult gut while Barrett’s esophagus shows high HOXA13 expression in stem cells and their progeny. HOXA13 overexpression appears sufficient to explain both the phenotype (through downregulation of the epidermal differentiation complex) and the oncogenic potential of Barrett’s esophagus. Intriguingly, employing a mouse model that contains a reporter coupled to the HOXA13 promotor we identify single HOXA13-positive cells distally from the physiological esophagus, which is mirrored in human physiology, but increased in BE. Additionally, we observe that HOXA13 expression confers a competitive advantage to cells. We thus propose that Barrett’s esophagus and associated esophageal adenocarcinoma is the consequence of expansion of this gastro-esophageal HOXA13-expressing compartment following epithelial injury.
2021-04-24 | GSE173166 | GEO
Project description:Transcriptional profiling of mouse embryonic stem cells comparing control (dCas9 transfected) ES cells with ES cells transfected with a Hottip promoter gRNAs and Hoxa13 promoter gRNAs along with dCAs9-VP160. Goal was to determine the effects of activation of Hottip lncRNA and Hoxa13 on expression of Hox genes
2017-03-10 | GSE95064 | GEO
Project description:Barrett’s esophagus in gastrointestinal reflux patients constitutes a columnar epithelium with distal characteristics, prone to progress to esophageal adenocarcinoma. HOX genes are known mediators of position-dependent morphology. Here we show HOX collinearity in the adult gut while Barrett’s esophagus shows high HOXA13 expression in stem cells and their progeny. HOXA13 overexpression appears sufficient to explain both the phenotype (through downregulation of the epidermal differentiation complex) and the oncogenic potential of Barrett’s esophagus. Intriguingly, employing a mouse model that contains a reporter coupled to the HOXA13 promotor we identify single HOXA13-positive cells distally from the physiological esophagus, which is mirrored in human physiology, but increased in BE. Additionally, we observe that HOXA13 expression confers a competitive advantage to cells. We thus propose that Barrett’s esophagus and associated esophageal adenocarcinoma is the consequence of expansion of this gastro-esophageal HOXA13-expressing compartment following epithelial injury.
2021-04-24 | GSE173168 | GEO