Filters
Technology
Platform
GSE64835
Mus musculus
2 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Stem and progenitor cells are the critical units for tissue maintenance, regeneration, and repair. The activation of regenerative events in response to tissue injury has been correlated with mobilization of tissue-resident progenitor cells, which is functional to the wound healing process. However, until now there has been no evidence for the presence of cells with a healing capacity circulating in healthy conditions. We identified a rare cell population present in the peripheral blood of healthy mice that actively participates in tissue repair. These Circulating cells, with a Homing ability and involved in the Healing process (CH cells), were identified by an innovative flowcytometry strategy as small cells not expressing CD45 and lineage markers. Their transcriptome profile revealed that CH cells are unique and present a high expression of key pluripotency- and epiblast-associated genes. More importantly, CH-labeled cells derived from healthy Red Fluorescent Protein (RFP)-transgenic mice and systemically injected into syngeneic fractured wild-type mice migrated and engrafted in wounded tissues, ultimately differentiating into tissue-specific cells. Accordingly, the number of CH cells in the peripheral blood rapidly decreased following femoral fracture. These findings uncover the existence of constitutively circulating cells that may represent novel, accessible, and versatile effectors of therapeutic tissue regeneration.
Publication Title
Identification of a New Cell Population Constitutively Circulating in Healthy Conditions and Endowed with a Homing Ability Toward Injured Sites.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The classical concept of bone marrow-derived mesenchymal stem cells (BM-MSC), intended as a uniform, broad potent population, is progressively being substituted by the idea that the bone marrow harbors heterogeneous populations of non-hematopoietic stem cells. This in vivo heterogeneity is also amplified by the different experimental strategies used to isolate/culture them. Among the exogenous factors described to affect MSC in vitro growth, basic-fibroblast growth factor (bFGF) is one of the most common growth factors used to expand stem cells. Moreover, it has been reported that its signaling is associated with the mainteinance of stemness of a variety of stem cells, included MSC. Using an ectopic model of bone regeneration, we have previously described that the implantation of cells with different commitment levels, differentially influences the capacity to recruit host cells, activating endogenous regenerative mechanisms. Due to its properties, we here demonstrate that the addition of bFGF to primary BM cultures, leads to the selection of specific subpopulations able to induce a different host regenerative response, when in vivo implanted in association with suitable ceramic scaffolds. Moreover, taking advantage of a multiparametric and comparative genomic and proteomic approach, it has been evaluated how different culture conditions combine to bring about appreciable changes in the secretome of the cells, that consequently influence their in vivo regenerative behaviour. The full comprehension of the regulatory mechanisms that rule the host response depending on the type and differentiative stage of the transplanted cells could help us to develop novel clinical strategies where host cells could directly contribute to regenerate the appropriate tissue.
Publication Title
The role of bFGF on the ability of MSC to activate endogenous regenerative mechanisms in an ectopic bone formation model.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 298 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Skin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. Like other tissues, skin is subject to temporal fluctuations in physiological responses under both homeostatic and stressed states. To gain insight into these fluctuations, we investigated the role of the circadian clock in the transcriptional regulation of human epidermal samples collected in a time-ordered fashion. We also determined whether this circadian patterning could be applied to unordered (i.e., randomly collected) human epidermal samples. The purpose of this study was to gain insight into the evolutionarily-conserved rhythmic patterns of the circadian transcriptome in human skin and how it relates to published transcriptomes from other human tissues.
Publication Title
Population-level rhythms in human skin with implications for circadian medicine.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Small nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs (scaRNAs) are non-coding RNAs involved in the maturation of other RNA molecules and generally located in the introns of host genes. It is now emerging that altered sno/scaRNAs expression may play a pathological role in cancer. This study elucidates the patterns of sno/scaRNAs expression in multiple myeloma (MM), by profiling puri?ed malignant plasma cells from 55 MMs, 8 secondary plasma cell leukemias (sPCL) and 4 normal controls. Overall, a global sno/scaRNAs down-regulation was found in MMs and at more extent in sPCLs compared to normal plasma cells. Whereas SCARNA22 resulted the only sno/scaRNA characterizing the TC4 MM, TC2 group displayed a distinct sno/scaRNA signature overexpressing members of SNORD115 and SNORD116 families located in a region finely regulated by imprinting mechanism at 15q11. However, the imprinting center resulted overall hypomethylated in MMs independently of the SNORD115 and SNORD116 expression levels. Finally, integrative analyses with available gene expression and genome-wide data revealed the occurrence of significant sno/scaRNAs/host genes co-expression and the putative influence of allelic imbalances on specific snoRNAs expression. Our data extend the current view of sno/scaRNAs deregulation in cancer and add novel information into the bio-molecular complexity of plasma cell dyscrasias.
Publication Title
The expression pattern of small nucleolar and small Cajal body-specific RNAs characterizes distinct molecular subtypes of multiple myeloma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
We previously found that KLF4, a gene highly expressed in adult prostate stem cells, blocks the progression of indolent intraepithelial prostatic lesions into aggressive and rapidly growing tumors. To test whether this anti-cancer effect of KLF4 can also prevent prostate cancer-induced damage to the bone, we ablated KLF4 in human PC3 prostate cancer cells using CRISPR/Cas9-mediated genome editing and compared their behavior to null cells transduced with a DOX inducible KLF4 expression system. KLF4 re-expression inhibited growth of PC3 null cells in monolayer and as colonies in soft agar in a dose-dependent manner. When injected into the mouse femurs, PC3 null cells proliferated rapidly, forming very large, invasive and osteolytic tumors. Induction of KLF4 expression in PC3 null cells immediately after their intra-femoral inoculation blocked the development of tumors while preserving the normal bone architecture. KLF4 re-expression in established PC3 bone tumors inhibited osteolytic effects of PC3 null cells, preventing bone fractures and inducing a significant osteogenic response with regions of new bone formation. Transcriptome analyses of PC3 cells with no or high KLF4 expression revealed KLF4-dependent osteolytic or osteogenic transcriptional programs, respectively. Importantly, these KLF4-dependent functions significantly overlapped with metastatic prostate cancers in patients. Overall design: Uninfected PC3 KLF4 wild-type cells and uninfected PC3 KLF4 null cells were grown for 48 hours and collected for RNA extraction. Another cohort of PC3 KLF4 null cells was infected with lentiviruses expressing a DOX inducible KLF4 expression construct (BFP-T2A-hKLF4) or the control empty vector (BFP-T2A). After 48 hours, DOX (10 ng/ml) was added to the culture medium to induce KLF4 expression. Control and KLF4-overexpressing cells were collected for RNA extraction after a 48-hour incubation with DOX. Total RNA was extracted using the RNeasy kit (Qiagen, CA, USA). RNA-Seq libraries were prepared with the TruSeq sample preparation kit (Illumina, CA, USA).
Publication Title
KLF4 as a rheostat of osteolysis and osteogenesis in prostate tumors in the bone.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Differentially expressed genes along the paraxial mesoderm of 12 somite stage zebrafish embryos are identified
Publication Title
Spatiotemporal compartmentalization of key physiological processes during muscle precursor differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 246 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 93 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The identification of deregulated miRNA in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In the present study, we take virtue of in silico integrative genomics analysis to generate an unprecedented global view of the transcriptional regulatory networks modulated in MM to define microRNAs impacting in regulatory circuits with potential functional and clinical relevance. miRNA and gene expression profiles in two large representative MM datasets, available from retrospective and prospective clinical trials and encompassing a total of 249 patients at diagnosis, were analyzed by means of two robust computational procedure to identify (i) relevant miRNA/transcription factors/target gene circuits in the disease and (ii) highly modulated miRNA-gene networks in those pathways enriched with miRNA-target gene interactions in specific MM subgroups. The analysis reinforced the pivotal role the miRNA cluster miR-99b/let-7e/miR-125a, specifically deregulated in MM patients with t(4;14) translocation, and disentangled its major relationships with transcriptional relevance. Integrated pathway analyses performed on the expression data of the MM patients stratified according to t(4;14) further allowed to define the pathway composed by the interactions that mainly characterize this MM subset and unravel connected pathways with putative role in the tumor biology.
Publication Title
Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 27 Downloadable Samples
- Illumina HiSeq 2000
Description
Multiple myeloma (MM) is a malignant proliferation of bone marrow plasma cells (PCs) characterized by highly heterogeneous genetic background and clinical course, and whose pathogenesis remains largely unknown. Long ncRNAs (lncRNAs) are a large class of non-protein-coding RNA, involved in many physiological cellular and genomic processes as well as in carcinogenesis, cancer metastasis and invasion. Although still in its infancy, the knowledge of the role of lncRNAs in MM is progressively expanding. Besides studies on selected candidates, lncRNAs expression at genome-wide transcriptome level is confined to microarray technologies, thus investigating a limited collection of transcripts. Herein, we assessed the lncRNAs expression profiling by RNA-sequencing in a cohort of 30 MM patients, aimed at defining a comprehensive catalogue of lncRNAs specifically associated with the main MM molecular subgroups and genetic alterations. We identified 391 deregulated lncRNAs, 67% of which were also detectable and validated by whole-transcript microarrays. In addition, we identified a list of lncRNAs, with potential relevance in MM, co-expressed and in close proximity to genes that might undergo a cis-regulatory relationship. Overall design: Total RNA samples from highly purified plasma cells of 30 MM cases at onset
Publication Title
Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The identification of deregulated miRNA in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In the present study, we take virtue of in silico integrative genomics analysis to generate an unprecedented global view of the transcriptional regulatory networks modulated in MM to define microRNAs impacting in regulatory circuits with potential functional and clinical relevance. miRNA and gene expression profiles in two large representative MM datasets, available from retrospective and prospective clinical trials and encompassing a total of 249 patients at diagnosis, were analyzed by means of two robust computational procedure to identify (i) relevant miRNA/transcription factors/target gene circuits in the disease and (ii) highly modulated miRNA-gene networks in those pathways enriched with miRNA-target gene interactions in specific MM subgroups. The analysis reinforced the pivotal role the miRNA cluster miR-99b/let-7e/miR-125a, specifically deregulated in MM patients with t(4;14) translocation, and disentangled its major relationships with transcriptional relevance. Integrated pathway analyses performed on the expression data of the MM patients stratified according to t(4;14) further allowed to define the pathway composed by the interactions that mainly characterize this MM subset and unravel connected pathways with putative role in the tumor biology.
Publication Title
Disentangling the microRNA regulatory milieu in multiple myeloma: integrative genomics analysis outlines mixed miRNA-TF circuits and pathway-derived networks modulated in t(4;14) patients.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples