Tumor growth is associated with a profound alteration of myelopoiesis, leading to recruitment of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs). Immuno-regulatory activity of both tumor-induced and BM-derived MDSCs (by GM-CSF and IL-6 treatment) was entirely dependent on C/EBP transcription factor (TF), a key component of the emergency myelopoiesis triggered by stress and inflammation. We used miR expression analysis to identify miRs which could drive MDSC recruitment/generation/activity by modulating specific TFs and pathway. In particular, we identified a miR signature of 79 miR differentially expressed between not suppressive CD11b+ cells and CD11b+ isolated from tumor mass and spleen of tumor-bearing mice. Moreover on the same samples we profiled gene expression with Affymetrix microarrays to perform an integrated analysis of mirna and gene expression.
miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis.
Specimen part, Disease, Disease stage, Cell line
View SamplesPurpose: Investigate the molecular determinants of retinal regeneration in adult vertebrates by analyzing the gene expression profiles of control and post-lesion retina of adult zebrafish, a system that regenerates following injury. Methods: Gene expression profiles of zebrafish retina and brain were determined with DNA microarray, RT-PCR, and real-time quantitative PCR analyses. Damaged retinas and their corresponding controls were analyzed 2-5 days post-lesion (acute injury condition) or 14 d post-lesion (cell regeneration condition). Results: Expected similarities and differences in the gene expression profile of zebrafish retina and brain were observed, confirming the applicability of the gene expression techniques. Mechanical lesion of retina triggered significant, time-dependent changes in retinal gene expression. The induced transcriptional changes were consistent with cellular phenomena known to occur, in a time-dependent manner, subsequent to retinal lesion, including cell cycle progression, axonal regeneration, and regenerative cytogenesis. Conclusions: The results indicate that retinal regeneration in adult zebrafish involves a complex set of induced, targeted changes in gene transcription, and suggest that these molecular changes underlie the ability of the adult vertebrate retina to regenerate. Keywords: time course; injury response; cellular correlation Control brain and retina (unlesioned); Control and lesioned retina (matched animals, at least n = 8 for each condition).
Gene expression profiles of intact and regenerating zebrafish retina.
Specimen part, Subject, Time
View SamplesReprogramming of somatic cells is a valuable tool to understand the mechanisms of regaining pluripotency and further opens up the possibility of generating patient-specific pluripotent stem cells. Reprogramming of mouse and human somatic cells into pluripotent stem cells, designated as induced pluripotent stem (iPS) cells, has been possible with the expression of the transcription factor quartet Oct4 (also known as Pou5f1), Sox2, c-Myc, and Klf4. Considering that ectopic expression of c-Myc causes tumourigenicity in offspring and retroviruses themselves can cause insertional mutagenesis, the generation of iPS cells with a minimal number of factors may hasten the clinical application of this approach. Here, we show that adult mouse neural stem cells express higher endogenous levels of Sox2 and c-Myc than embryonic stem cells, and that exogenous Oct4 together with either Klf4 or c-Myc are sufficient to generate iPS cells from neural stem cells. These two-factor (2F) iPS cells are similar to embryonic stem cells at the molecular level, contribute to development of the germ line, and form chimeras. We propose that, in inducing pluripotency, the number of reprogramming factors can be reduced when using somatic cells that endogenously express appropriate levels of complementing factors.
Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors.
No sample metadata fields
View SamplesOld C57BL/6 mice cannot mount an effective innate immune response
Aged mice are unable to mount an effective myeloid response to sepsis.
Specimen part, Treatment, Time
View SamplesThe four transcription factors Oct4, Sox2, Klf4, and c-Myc can induce pluripotency in mouse and human fibroblasts. We previously described direct reprogramming of adult mouse neural stem cells (NSCs) by Oct4 and either Klf4 or c-Myc. NSCs endogenously express Sox2, c-Myc, and Klf4 as well as several intermediate reprogramming markers. Here we report that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs. These one-factor induced pluripotent stem (1F iPS) cells are similar to embryonic stem cells in vitro and in vivo. Not only can these cells be efficiently differentiated into NSCs, cardiomyocytes and germ cells in vitro, but they are also capable of teratoma formation and germline transmission in vivo. Our results demonstrate that Oct4 is required and sufficient to directly reprogram NSCs to pluripotency.
Oct4-induced pluripotency in adult neural stem cells.
No sample metadata fields
View SamplesThe polytrauma (PT) murine model has unique transcriptomic responses 2 hrs, 1 day and 3 days after injury. We determined with this clinically relevant model that the increased morbidity in the elderly is secondary to a failure of bone marrow progenitors, blood neutrophils, and bronchoalveolar lavage cells to initiate and complete an 'emergency myelopoietic' response, engendering myeloid cells that fail to clear secondary infection. In addition, the elderly appear unable to effectively resolve their inflammatory response to severe injury.
A Detailed Characterization of the Dysfunctional Immunity and Abnormal Myelopoiesis Induced by Severe Shock and Trauma in the Aged.
Sex, Specimen part, Treatment
View SamplesWe employed GeneChip analysis to investigate the global gene expression profiles of neutrophils from BM
Neutrophil priming occurs in a sequential manner and can be visualized in living animals by monitoring IL-1β promoter activation.
Specimen part
View SamplesHistone deacetylases (Hdac) remove acetyl groups from proteins, influencing global and specific gene expression. Hdacs control inflammation, as shown by Hdac inhibitor-dependent protection from DSS-induced murine colitis. While tissue-specific Hdac knockouts show redundant and specific functions, little is known of their intestinal epithelial cell (IEC) role. We have shown previously that dual Hdac1/Hdac2 IEC-specific loss disrupts cell proliferation and determination, with decreased secretory cell numbers and altered barrier function. We thus investigated how compound Hdac1/Hdac2 or Hdac2 IEC-specific deficiency alters the inflammatory response. Floxed Hdac1 and Hdac2 and villin-Cre mice were interbred. Compound Hdac1/Hdac2 IEC-deficient mice showed chronic basal inflammation, with increased basal Disease Activity Index (DAI) and deregulated Reg gene colonic expression. DSS-treated dual Hdac1/Hdac2 IEC-deficient mice displayed increased DAI, histological score, intestinal permeability and inflammatory gene expression. In contrast to double knockouts, Hdac2 IEC-specific loss did not affect IEC determination and growth, nor result in chronic inflammation. However, Hdac2 disruption protected against DSS colitis, as shown by decreased DAI, intestinal permeability and caspase-3 cleavage. Hdac2 IEC-specific deficient mice displayed increased expression of IEC gene subsets, such as colonic antimicrobial Reg3b and Reg3g mRNAs, and decreased expression of immune cell function-related genes. Our data show that Hdac1 and Hdac2 are essential IEC homeostasis regulators. IEC-specific Hdac1 and Hdac2 may act as epigenetic sensors and transmitters of environmental cues and regulate IEC-mediated mucosal homeostatic and inflammatory responses. Different levels of IEC Hdac activity may lead to positive or negative outcomes on intestinal homeostasis during inflammation
The acetylome regulators Hdac1 and Hdac2 differently modulate intestinal epithelial cell dependent homeostatic responses in experimental colitis.
Specimen part
View SamplesTo test the regulatory effects of Dmrt5 on gene expression, we designed tetracycline inducible lines of Dmrt5 transgenic mouse ESCs. Overexpression of Dmrt5 was induced upon addition of Doxycycline (Dox). To evaluate the effects of Dmrt5 on gene expression in different stages of in vitro differentiated NPC derived from mouse embryonic stem cells (ESC), we analyzed gene expression profiles at differentiation day 7 and day 9 with or without Dox. The data revealed that overexpression of Dmrt5 in in vitro differentiated neural progenitor cells (NPC) regulates gene expression. Addition of Dox to the medium of the control cell line rtTA did not significantly alter gene expression profile, demonstrating that the observed effects were through induction of Dmrt5, but not simply through Dox.
Doublesex and mab-3-related transcription factor 5 promotes midbrain dopaminergic identity in pluripotent stem cells by enforcing a ventral-medial progenitor fate.
Cell line, Treatment
View SamplesThe pathogenic mechanisms of common kidney glomerular diseases, including the vast majority of cases of proteinuria, remain unknown.
Glomerular transcriptome changes associated with lipopolysaccharide-induced proteinuria.
No sample metadata fields
View Samples