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GSE54044
Mus musculus
15 Downloadable Samples
Description
The zinc finger factor Insm1 is known to regulate differentiation of pancreatic cells during development, Here we show that Insm1 is essential for the maintenance of functionally mature pancreatic cells in mice.
Publication Title
Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β-cell function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Description
We have recently shown a remarkable regenerative capacity of the prenatal heart using a genetic model of mosaic mitochondrial dysfunction in mice. This model is based on inactivation of the X-linked gene encoding holocytochrome c synthase (Hccs) specifically in the developing heart. Loss of HCCS activity results in respiratory chain dysfunction, disturbed cardiomyocyte differentiation and reduced cell cycle activity. The Hccs gene is subjected to X chromosome inactivation, such that in females heterozygous for the heart conditional Hccs knockout approximately 50% of cardiac cells keep the defective X chromosome active and develop mitochondrial dysfunction while the other 50% remain healthy. During heart development, however, the contribution of HCCS deficient cells to the cardiac tissue decreases from 50% at midgestation to 10% at birth. This regeneration of the prenatal heart is mediated by increased proliferation of the healthy cardiac cell population, which compensate for the defective cells and allow the formation of a fully functional heart at birth. Here we performed microarray expression ananlyses on 13.5 dpc control and heterozygous Hccs knockout hearts to identify molecular mechanisms that drive embryonic heart regeneration.
Publication Title
Embryonic cardiomyocytes can orchestrate various cell protective mechanisms to survive mitochondrial stress.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Histone 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
Publication Title
The acetylome regulators Hdac1 and Hdac2 differently modulate intestinal epithelial cell dependent homeostatic responses in experimental colitis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
Description
Maintenance of the blood system is dependent on dormant haematopoietic stem cells (HSCs) with long-term self-renewal capacity. Upon injury these cells are induced to proliferate in order to quickly re-establish homeostasis. The signalling molecules promoting the exit of HSCs out of the dormant stage remain largely unknown. Here we show that in response to treatment of mice with interferon-alpha (IFN), HSCs efficiently exit G0 and enter an active cell cycle. HSCs respond to IFN treatment by increased phosphorylation of STAT1 and PKB/Akt, expression of IFN target genes and up-regulation of stem cell antigen-1 (Sca-1). HSCs lacking either the interferon-/ receptor (IFNAR), STAT1 or Sca-1 are insensitive to IFN stimulation, demonstrating that STAT1 and Sca-1 mediate IFN induced HSC proliferation. Although dormant HSCs are resistant to the anti-proliferative chemotherapeutic agent 5-FU1, HSCs pre-treated (primed) with IFN and thus induced to proliferate are efficiently eliminated by 5-FU exposure in vivo. Conversely, HSCs chronically activated by IFN are functionally compromised and are rapidly out competed by non-activatable IFNAR-/- cells in competitive repopulation assays. In summary, while chronic activation of the IFN pathway in HSCs impairs their function, acute IFN treatment promotes the proliferation of dormant HSCs in vivo. These data may help to clarify the so far unexplained clinical effects of IFN on leukemic cells and raise the possibility for novel applications of type I interferons to target cancer stem cells.
Publication Title
IFNalpha activates dormant haematopoietic stem cells in vivo.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 3 Downloadable Samples
Description
Loss of muscle mass occurs in a variety of diseases including cancer, chronic heart failure, AIDS, diabetes and renal failure, often aggravating pathological progression. Preventing muscle wasting by promoting muscle growth has been proposed as a possible therapeutic approach. Myostatin is an important negative modulator of muscle growth during myogenesis and myostatin inhibitors are attractive drug targets. However, the role of the myostatin pathway in adulthood and the transcription factors involved in the signaling are unclear. Moreover recent results confirm that other TGF members control muscle mass. Using genetic tools we perturbed this pathway in adult myofibers, in vivo, to characterize the downstream targets and their ability to control muscle mass. Smad2 and Smad3 are the transcription factors downstream of myostatin/TGF and induce an atrophy program which is MuRF1 independent and requires FoxO activity. Furthermore Smad2/3 inhibition promotes muscle hypertrophy independent of satellite cells but partially dependent of mTOR signalling. Thus myostatin and Akt pathways cross-talk at different levels. These findings point to myostatin inhibitors as good drugs to promote muscle growth during rehabilitation especially when they are combined with IGF1-Akt activators.
Publication Title
Smad2 and 3 transcription factors control muscle mass in adulthood.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Description
The skin interfollicular epidermis (IFE) is the first barrier against the external environment and its maintenance is critical for survival. Two seemingly opposite theories have been proposed to explain IFE homeostasis. One posits that IFE is maintained by a long-lived slow-cycling stem cell (SC) population that give rise to short-lived transit-amplifying (TA) cell progeny, while the other suggests that homeostasis is achieved by a single committed progenitor (CP) that balances stochastic fate. Here, we probed the cellular heterogeneity within the IFE using two different inducible CREER targeting IFE progenitors. Quantitative analysis of clonal fate data and proliferation dynamics demonstrate the existence of two distinct proliferative cell compartments composed of slow-cycling SC and CP, both of which undergo population asymmetric self-renewal. However, following wounding, only SCs contribute substantially to the repair and long-term regeneration of the tissue, while CP cells make a minimal and transient contribution.
Publication Title
Distinct contribution of stem and progenitor cells to epidermal maintenance.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nanoemulsion mucosal adjuvant uniquely activates cytokine production by nasal ciliated epithelium and induces dendritic cell trafficking.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Antigen uptake, processing and presentation by dendritic cells are regulated by complex intra- and inter-cellular signalling events. Typical vaccine adjuvants lead to the transcription of pro-inflammatory cytokines and chemokines which relate to immune induction.
Publication Title
Nanoemulsion mucosal adjuvant uniquely activates cytokine production by nasal ciliated epithelium and induces dendritic cell trafficking.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Mouse back skin was disassociated to single cells, sorted by cell surface markers and tested by microarrray
Publication Title
Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
Description
We used microarrays to detail the global programme of gene expression underlying the effect of sleep deprivation in the mouse hippocampus and identified distinct classes of regulated genes during this process.
Publication Title
Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples