Current human reproductive risk assessment methods rely on semen and serum hormone analyses, which are not easily comparable to the histopathological endpoints and mating studies used in animal testing. Because of these limitations, there is a need to develop universal evaluations that reliably reflect male reproductive function. We hypothesized that toxicant-induced testicular injury can be detected in sperm using mRNA transcripts as indicators of insult. To test this, we exposed adult male Fischer 344 rats to low doses of model testicular toxicants and classically characterized the testicular injury while simultaneously evaluating sperm mRNA transcripts from the same animals. Overall, this study aimed to: 1) identify sperm transcripts altered after exposure to the model testicular toxicant, 2,5-hexanedione (HD) using microarrays; 2) expand on the HD-induced transcript changes in a comprehensive time course experiment using qRT-PCR arrays; and 3) test these injury indicators after exposure to another model testicular toxicant, carbendazim (CBZ). Microarray analysis of HD-treated adult Fischer 344 rats identified 128 altered sperm mRNA transcripts when compared to control using linear models of microarray analysis (q < 0.05). All transcript alterations disappeared after 3 months of post-exposure recovery. In the time course experiment, time-dependent alterations were observed for 12 candidate transcripts selected from the microarray data based upon fold change and biological relevance, and 8 of these transcripts remained significantly altered after the 3-month recovery period (p < 0.05). In the last experiment, 8 candidate transcripts changed after exposure to CBZ (p < 0.05). The two testicular toxicants produced distinct molecular signatures with only 4 overlapping transcripts between them, each occurring in opposite directions. Overall, these results suggest that sperm mRNA transcripts are indicators of low dose toxicant-induced testicular injury in the rat.
Sperm mRNA transcripts are indicators of sub-chronic low dose testicular injury in the Fischer 344 rat.
Specimen part, Treatment
View SamplesGenes specific to Sox9+ pancreatic progenitors were identified by comparing the gene expression in embryonic and adult Sox9+ cells.
A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation.
Specimen part
View SamplesSpinal cord injury leads to impaired motor and sensory functions. After spinal cord injury there is a an initial phase of hypo-reflexia followed by a developing hyper-reflexia, often termed spasticity. Previous studies have suggested a relationship between the reappearence of plateau potentials in motor neurons and the development of spasticity after spinalizaion. To understand the moleclar mechanism behind this pheneomona we examined the transcriptional response of the motor neurons after spinal cord injury as it progress over time.
Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury.
Sex, Specimen part
View SamplesThe present study was designed to test the hypothesis that limited growth of the fetal liver in the model of maternal fasting is independent of well-characterized signaling mechanisms that are known to regulate somatic growth in adult animals.
Regulation of fetal liver growth in a model of diet restriction in the pregnant rat.
Specimen part, Treatment
View SamplesSequencing of 5' ends of RNA molecules from control and exosome-depleted HeLa-S3 cells. Overall design: CAGE library construction from RNA extracted from control and exosome-depleted cells.
Nuclear stability and transcriptional directionality separate functionally distinct RNA species.
No sample metadata fields
View SamplesGene expression programs change during cellular transitions. It is well established that a network of transcription factors and chromatin modifiers regulate RNA levels during embryonic stem cell (ESC) differentiation, but the full impact of post-transcriptional processes remains elusive. While cytoplasmic RNA turnover mechanisms have been implicated in differentiation, the contribution of nuclear RNA decay has not been investigated. Here, we differentiate mouse ESCs, depleted for the ribonucleolytic RNA exosome, into embryoid bodies to determine to which degree RNA abundance in the two states can be attributed to changes in transcription vs. RNA decay by the exosome. As a general observation, we find that exosome depletion mainly leads to the stabilization of RNAs from lowly transcribed loci, including several protein-coding genes. In particular, transcripts that are differentially expressed between states tend to be more exosome sensitive in the state where expression is low. We conclude that the RNA exosome contributes to down-regulation of transcripts with disparate expression, often in conjunction with transcriptional down-regulation. Overall design: CAGE experiments were carried out in mouse embryonic stem cells and embryoid bodies differentiated for three days upon depletion of RRP40 with shRNAs, using a scrambled shRNA as control. The experiments were performed in duplicates
The RNA exosome contributes to gene expression regulation during stem cell differentiation.
Specimen part, Cell line, Subject
View SamplesTo investigate genes possibly regulated by TTF-1 in small cell lung cancer cell lines, we compared gene expression profiles of NCI-H209 and Lu139 cell lines electroporated with control and TTF-1 siRNAs.
An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer.
Cell line
View SamplesOur strategy was to manipulate mTOR signaling in vivo, then characterize the transcriptome and translating mRNA in liver tissue. In adult rats, we used the non-proliferative growth model of refeeding after a period of fasting, and the proliferative model of liver regeneration following partial hepatectomy. We also studied livers from pre-term fetal rats (embryonic day 19-20) in which fetal hepatocytes are asynchronously proliferating. All three models employed rapamycin to inhibit mTOR signaling.
Profiling of the fetal and adult rat liver transcriptome and translatome reveals discordant regulation by the mechanistic target of rapamycin (mTOR).
Specimen part, Time
View SamplesLiver transplantation is the only therapeutic option for patients with end-stage liver disease. The shortage of donor organs has led to the search for alternative therapies to restore liver function and bridge patients to transplantation. Our previous work has shown that the proliferation of late gestation E19 fetal hepatocytes is mitogen-independent. This is manifested as differences in the control of ribosome biogenesis, global translation, cell cycle progression and gene expression. In the present study, we investigated whether E19 fetal hepatocytes would engraft and repopulate an injured adult liver.
Engraftment and Repopulation Potential of Late Gestation Fetal Rat Hepatocytes.
Specimen part
View SamplesInjury to anterior cruciate ligament (ACL) is common in young individuals and a frequent cause of functional instability and early onset of osteoarthritis. The healing potential of an injured ACL is known to decay over time. The molecular origin of this healing deficiency largely remains elusive but plausibly involves gene transcripts associated with tissue healing. To explore this possibility, we set out to identify transcript expression differences in injured ACL remnants recovered at the time of surgical reconstruction, via microarray (n=24) and RNA-seq (n=8) technologies in transcriptome profiling. We found that time-from-injury was an important determinant of changes in gene expression signatures predominately resulting in repression of several biological processes as identified by gene ontology. The most interesting observation was a time-dependent decline in the gene transcripts as well as the biological processes common to both microarray and RNA-seq analyses. Compared to acute tears, in chronic several important biological processes were namely extracellular matrix organization, angiogenesis, cell adhesion, wound healing, mesenchyme transition, and response to hypoxia. Furthermore, the cross-platform concordance in terms of differentially expressed transcripts or enriched pathways was linearly correlated (r=0.64). Microfluidic digital PCR confirmed the expression of selected differentially expressed transcripts. These intriguing findings suggest an initial attempt of the injured ACL to repair, which drops with time. These findings have implications for efforts to repair the ACL and may be relevant for its reconstruction. These findings also emphasize the utility of differentially expressed transcripts as prognostic biomarkers in patients with ACL injury. Overall design: Examination of transcript expression differences by time-from-injury in anterior cruciate ligament
Advantages of RNA-seq compared to RNA microarrays for transcriptome profiling of anterior cruciate ligament tears.
No sample metadata fields
View Samples