RNA-Seq defines novel genes, RNA processing patterns and enhancer maps for the early stages of nephrogenesis: Hox supergenes

Brunskill, Eric W.; Potter, S. Steven

doi:10.1016/j.ydbio.2012.05.030

Cited by 36 publications

(37 citation statements)

References 63 publications

(83 reference statements)

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“…In this regard, downmodulation of HOXD10 and HOXA9 could be involved in the maintenance of the epithelial phenotype and in the modulation of the immune response. The discrepancies between our data and those previously reported in relation to HOXB4, HOXC12, and HOXC13 may be due to the different techniques used, as well as to the new isoforms recently described (Brunskill and Potter, 2012).…”

Section: Discussioncontrasting

confidence: 99%

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

Alvarado-Ruíz¹,

Martínez-Silva²,

Torres-Reyes³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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HOX transcription factors are evolutionarily conserved in many different species and are involved in important cellular processes such as morphogenesis, differentiation, and proliferation. They have also recently been implicated in carcinogenesis, but their precise role in cancer, especially in cervical cancer (CC), remains unclear. In this work, using microarray assays followed by the quantitative polymerase chain reaction (qPCR), we found that the expression of 25 HOX genes was downregulated in CC derived cell lines compared with nontumorigenic keratinocytes. In particular, the expression of HOXA9 was observed as down-modulated in CCderived cell lines. The expression of HOXA9 has not been previously reported in CC, or in normal keratinocytes of the cervix. We found that normal CC from women without cervical lesions express HOXA9; in contrast, CC cell lines and samples of biopsies from women with CC showed significantly diminished HOXA9 expression. Furthermore, we found that methylation at the first exon of HOXA9 could play an important role in modulating the expression of this gene. Exogenous restoration of HOXA9 expression in CC cell lines decreased cell proliferation and migration, and induced an epithelial-like phenotype. Interestingly, the silencing of human papilloma virus (HPV) E6 and E7 oncogenes induced expression of HOXA9. In conclusion, controlling HOXA9 expression appears to be a necessary step during CC development. Further studies are needed to delineate the role of HOXA9 during malignant progression and to afford more insights into the relationship between downmodulation of HOXA9 and viral HPV oncoprotein expression during cercical cancer development.

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Section: Discussioncontrasting

confidence: 99%

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

Alvarado-Ruíz¹,

Martínez-Silva²,

Torres-Reyes³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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“…We observed that the Hox clusters displayed a number of interesting noncanonical splicing patterns, many of which we have previously described in the developing kidney (Brunskill and Potter, 2012). For example, in the WT uterus the last exon of Hoxd11 was frequently spliced to the last exon of Hoxd10, resulting in a frameshifted non-coding transcript (Fig.…”

Section: Rna-seq Analysis Validates the Microarray Changes And Revealmentioning

confidence: 53%

“…Data were analyzed in Avadis NGS as previously described (Brunskill and Potter, 2012) and deposited in the GEO database with accession number GSE42339.…”

Section: Gene Expression and Data Analysismentioning

confidence: 99%

Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts

et al. 2013

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SUMMARYHox genes are key regulators of development. In mammals, the study of these genes is greatly confounded by their large number, overlapping functions and interspersed shared enhancers. Here, we describe the use of a novel recombineering strategy to introduce simultaneous frameshift mutations into the flanking Hoxa9, Hoxa10 and Hoxa11 genes, as well as their paralogs on the HoxD cluster. The resulting Hoxa9,10,11 mutant mice displayed dramatic synergistic homeotic transformations of the reproductive tracts, with the uterus anteriorized towards oviduct and the vas deferens anteriorized towards epididymis. The Hoxa9,10,11 mutant mice also provided a genetic setting that allowed the discovery of Hoxd9,10,11 redundant reproductive tract patterning function. Both shared and distinct Hox functions were defined. Hoxd9,10,11 play a crucial role in the regulation of uterine immune function. Non-coding nonpolyadenylated RNAs were among the key Hox targets, with dramatic downregulation in mutants. We observed Hox cross-regulation of transcription and splicing. In addition, we observed a surprising anti-dogmatic apparent posteriorization of the uterine epithelium. In caudal regions of the uterus, the normal simple columnar epithelium flanking the lumen was replaced by a pseudostratified transitional epithelium, normally found near the more posterior cervix. These results identify novel molecular functions of Hox genes in the development of the male and female reproductive tracts.

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“…P4 RV cells were isolated as previously described (Brunskill and Potter, 2012b). We carried out RNA-seq gene expression profiling of 58 single cells.…”

Section: Single Cell Analysis Of the Renal Vesiclementioning

confidence: 99%

“…For example, by using Meis1-GFP, Tie2-GFP and Mafb-GFP mice, coupled with fluorescence-activated cell sorting (FACS), the glomerulus was subdivided into the mesangial, endothelial and podoctye constituent cell types (Brunskill et al, 2011a;Potter, 2010, 2012a). Additional transgenic GFP mice allowed the analysis of CM, renal vesicles and renin-producing cells (Brunskill and Potter, 2012b;Brunskill et al, 2011b).…”

Section: Introductionmentioning

confidence: 99%

Single cell dissection of early kidney development: multilineage priming

et al. 2014

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We used a single cell RNA-seq strategy to create an atlas of gene expression patterns in the developing kidney. At several stages of kidney development, histologically uniform populations of cells give rise to multiple distinct lineages. We performed single cell RNA-seq analysis of total mouse kidneys at E11.5 and E12.5, as well as the renal vesicles at P4. We define an early stage of progenitor cell induction driven primarily by gene repression. Surprising stochastic expression of marker genes associated with differentiated cell types was observed in E11.5 progenitors. We provide a global view of the polarized gene expression already present in the renal vesicle, the first epithelial precursor of the nephron. We show that Hox gene readthrough transcripts can be spliced to produce intergenic homeobox swaps. We also identify a surprising number of genes with partially degraded noncoding RNA. Perhaps most interesting, at early developmental times single cells often expressed genes related to several developmental pathways. This provides powerful evidence that initial organogenesis involves a process of multilineage priming. This is followed by a combination of gene repression, which turns off the genes associated with most possible lineages, and the activation of increasing numbers of genes driving the chosen developmental direction.

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RNA-Seq defines novel genes, RNA processing patterns and enhancer maps for the early stages of nephrogenesis: Hox supergenes

Cited by 36 publications

References 63 publications

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

HOXA9 is Underexpressed in Cervical Cancer Cells and its Restoration Decreases Proliferation, Migration and Expression of Epithelial-to-Mesenchymal Transition Genes

Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts

Single cell dissection of early kidney development: multilineage priming

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