We report the ability of the Drosha null/conditional-null mouse model to enable the identification of pri-miRNA transcripts. The conditional-null allele of Drosha phenocopies the null allele both in mESC and in mice, upon conversion to the null state with Cre. Overall design: Examination of the effects of Drosha deficiency in mouse embryonic stem cells.
microTSS: accurate microRNA transcription start site identification reveals a significant number of divergent pri-miRNAs.
No sample metadata fields
View SamplesInjuries to the anterior cruciate ligament (ACL) often result in post-traumatic osteoarthritis (PTOA). PTOA accounts for ~12% of all osteoarthritis (OA) cases, yet the mechanisms contributing to OA after joint injury are not well understood. To better understand the molecular mechanisms behind PTOA development following ACL injury, we profiled ACL injury-induced gene expression changes in knee joints of three mouse strains with varying susceptibility to PTOA: STR/ort (highly susceptible), C57BL/6 (moderately susceptible) and super-healer MRL/MpJ (not susceptible) and identified genes differentially expressed between these strains at 0-day [before injury], 1-day, 1-week, and 2-weeks post-injury. This study highlights many new potential therapeutic targets and OA biomarkers. Overall design: Comparative transcriptomics to understand the molecular changes associated with early stages of PTOA development in STR/ort, C57BL/6 and MRL/MpJ mice and to identify genes that contribute to increased OA susceptibility in STR/ort and resistance to PTOA in MRL/MpJ.
Comparative Transcriptomics Identifies Novel Genes and Pathways Involved in Post-Traumatic Osteoarthritis Development and Progression.
Age, Specimen part, Cell line, Treatment, Subject
View SamplesWNT signaling is critical in most aspects of skeletal development and homeostasis, and antagonists of WNT signaling are emergning as key regulatory proteins with great promise as therapeutic agents for bone disorders. Until recently Sost and its paralog Sostdc1 have been described as growth factors with highly restricted expression in the adult where Sost was assumed 'osteocyte-' and Sostdc1 'kidney-' specific. Here we show that these two proteins emerged throgh ancestral genome duplication and their expression patterns have diverged to span complimentary domains in most organ systems including musculoskeletal, cardiovascular, nervous, digestive, reproductive and respiratory. In the developing limb, Sost and Sostdc1 display dynamic expression patterns with Sost being restricted to the distal ectoderm and Sostdc1 to the proximal ectoderm and the mesenchyme.
Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent manner.
Specimen part
View SamplesDifferential gene expression analysis of parental and sub-lines of melanoma cell line resistant to F5 CTL lymphocyte
Molecular mechanism of MART-1+/A*0201+ human melanoma resistance to specific CTL-killing despite functional tumor-CTL interaction.
Cell line
View SamplesParathyroid hormone (PTH) and PTH-related protein (PTHrP) are involved in cachexia associated with chronic kidney disease and cancer respectively. Tumor-derived PTHrP triggers adipose tissue browning and thereby leads to wasting of fat tissue in tumor-bearing mice. Similarly, elevated in 5/6 nephrectomized mice, PTH stimulates adipose tissue browning and wasting. Mice lacking the PTH/PTHrP receptor in their fat tissue are resistant to wasting of both adipose tissue and skeletal muscle. Therefore, the PTH/PTHrP signaling in adipocytes should activate various pathways that contribute to hypermetabolism and muscle wasting.
PTH/PTHrP Receptor Mediates Cachexia in Models of Kidney Failure and Cancer.
Sex, Specimen part
View SamplesPanel of 53 melanoma cell lines were gene expression profiled by RNA-Seq for molecular classification Overall design: mRNA profiles of 53 melanoma cell lines
Interleukin 32 expression in human melanoma.
Disease, Disease stage, Cell line, Subject
View SamplesDuring gastrulation, epiblast cells are pluripotent and their fate is thought to be constrained principally by their position. Cell fate is progressively restricted by localised signalling cues from areas including the primitive streak (PS). However, it is unknown whether this restriction accompanies, at the single cell level, a reduction in potency. Investigation of these early transition events in vitro is possible via the use of Epiblast Stem Cells (EpiSCs), self-renewing pluripotent cell lines equivalent to the postimplantation epiblast. Strikingly, EpiSCs express various early lineage-specific markers in self-renewing conditions. However, it is unknown whether cells that express these markers are pluripotent, spontaneously differentiated, or biased towards specific lineages. Here we show that EpiSC are inherently heterogeneous and contain two major and mutually exclusive subpopulations with PS and neural characteristics respectively. Using differentiation assays and embryo grafting we demonstrate that PS-like EpiSCs are biased towards mesoderm and endoderm differentiation but they still retain their pluripotent character. The acquisition of a PS character by undifferentiated EpiSC is mediated by paracrine Wnt signalling. Elevation of Wnt activity promotes further restriction into PS-associated cell fates which occurs via the generation of distinct clonal mesendodermal and neuromesodermal precursors. Collectively, our data suggest that primed pluripotency encompasses a range of reversible lineage-biased states reflecting the birth of pioneer lineage precursors from a pool of uncommitted EpiSCs similar to the earliest cell fate restriction events taking place in the gastrula-stage epiblast.
Distinct Wnt-driven primitive streak-like populations reflect in vivo lineage precursors.
Sex, Specimen part
View SamplesBone mineral density and structure candidate gene analysis in alcohol-non-preferring (NP), alcohol-preferring (P), congenic NP (NP.P) and congenic P (P.NP) rats
Identification of genes influencing skeletal phenotypes in congenic P/NP rats.
No sample metadata fields
View SamplesFemoral neck bone mineral density and structure candidate gene analysis in Fischer 344 (F344) and Lewis (LEW) rats
Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral neck.
No sample metadata fields
View Samples