Filters
Technology
Platform
SRP103188
Homo sapiens
13 Downloadable Samples
Description
Here we propose the direct conversion of human somatic cells into naive induced pluripotent cells (niPSC). Dataset: 7 expanded niPSC lines (4 from BJ cells, 1 from HFF-1, 1 from WI38, 1from IMR90), 1 freshly-isolated primary colonies of niPSC from BJ, 1 established naive embryonic line H9, 1 primed induced pluripotent cell line (from BJ), 1 sample of BJ fibroblasts, 1 sample of WI38 fibroblasts, 1 sample IMR90 fibroblasts.
Publication Title
Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
In addition to lipid second messengers derived from the plasma membrane, increasing evidence supports the existence of nuclear lipid-dependent signaling networks. Diacylglycerol is a key second messenger, generated at the nuclear level, which is metabolized by diacylglycerol kinases (DGKs). It has been demonstrated that nuclear DGK- negatively regulates cell cycle progression. The aim of this study was to identify key determinants of nuclear DGK--dependent cell cycle arrest in C2C12 mouse myoblasts. Using DNA microarrays, Real-Time RT-PCR and western blot, we demonstrated that nuclear DGK- downregulated the expression of cyclin D1 and increased the expression of TIS21/BTG2/PC3, a transcriptional regulator of cyclin D1 with a strong anti-proliferative function. Overexpression of TIS21/BTG2/PC3 blocked the cells in G1 phase of the cell cycle and decreased the levels of Ser807/811 phosphorylated retinoblastoma protein, similarly to overexpression of DGK-. Moreover, during myogenic differentiation of C2C12 cells, we showed an increase of TIS21/BTG2/PC3 expression and a decrease in cyclin D1 levels. siRNA downregulation of TIS21/BTG2/PC3 impaired myogenic differentiation by opposing cell cycle arrest. In summary, these data identify TIS21/BTG2/PC3 and cyclin D1 as downstream effectors of the nuclear DGK- and highlight the importance of this DGK isoform in the regulation of myoblast proliferation and differentiation.
Publication Title
TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-zeta-dependent cell cycle arrest.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The thrombopoietin/MPL axis is activated in the Gata1<sup>low</sup> mouse model of myelofibrosis and is associated with a defective RPS14 signature.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Myelofibrosis (MF) is caused by genetic abnormalities involving the thrombopoietin (TPO)/MPL/JAK2 axis. Furthermore MF patients have elevated serum TPO levels. MF is also associated with reduced GATA1 content in MK suggesting that this abnormality represents a phenotypic modifier. In 2014, Dr. Crispino suggested that in MF abnormal TPO signaling induces a ribosomal deficiency hampering GATA1 mRNA translation in MK. Support for MK GATA1 deficiency as phenotypic modifier in MF was provided by the observation that mice carrying the Gata1low mutation reducing Gata1 transcription in MK develop myelofibrosis. Since reduced RBC half-life subject these mice to continuous erythroid stress, we investigated the TPO/Mpl axis in this model. In Gata1low and wild-type mice, TPO mRNA was expressed by bone marrow (BM), spleen and liver. The greatest expression (by 300-fold) was detected in liver. Gata1low livers expressed TPO mRNA levels 6-fold greater than wild-type livers. TPO protein was detected in BM, spleen, liver and peritoneum washes and plasma. The greatest levels where detected in plasma. Gata1low plasma contained TPO levels 2-fold lower than wild-type plasma, but 2-times greater than plasma from bleed wild-type mice and Mplnull mice with similar thrombocytopenia, suggesting that TPO is overproduced in Gata1low mice. JAK2 and STAT5 were easily detected in Gata1low BM bur barely detectable in wild-type BM, suggesting that in the former MPL is prompt to signaling activation. Furthermore, Gata1low LSK expressed levels of Mpl mRNA 3-times greater than wild-type cells but expressed cell-surface levels of MPL 2-times lower than wild-type cells and similar to those on LSK from TPO-treated wild-type mice, suggesting that MPL is down-modulated in Gata1low LSK. The Crispinos hypothesis that in MF activation of TPO/MPL/JAK2 induces a ribosomal deficiency hampering GATA1 mRNA translation and the realization that this axis is activated in Gata1low mice made us question the original hypothesis that reduced content of GATA1 in Gata1low MK results from deletion of lineage-specific enhancers. Microarray analyses indeed identified that Gata1low BM express a discordant ribosome signature including reduced expression of RPS24 and RPS36A, two genes mutated in Diamond Blackfan Anemia, a disease characterized by inefficient GATA1 mRNA translation. Electron microscopy identified that the cytoplasm of Gata1low MK contained poorly developed endoplasmic reticulum with rare polysomes. In conclusion, these results validate the Gata1low model as a MF model by indicating that these mice express an activated TPO/MPL axis and an abnormal ribosomal signature which may reduce efficiency of Gata1 mRNA translation.
Publication Title
The thrombopoietin/MPL axis is activated in the Gata1<sup>low</sup> mouse model of myelofibrosis and is associated with a defective RPS14 signature.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Myelofibrosis (MF) is caused by genetic abnormalities involving the thrombopoietin (TPO)/MPL/JAK2 axis. Furthermore MF patients have elevated serum TPO levels. MF is also associated with reduced GATA1 content in MK suggesting that this abnormality represents a phenotypic modifier. In 2014, Dr. Crispino suggested that in MF abnormal TPO signaling induces a ribosomal deficiency hampering GATA1 mRNA translation in MK. Support for MK GATA1 deficiency as phenotypic modifier in MF was provided by the observation that mice carrying the Gata1low mutation reducing Gata1 transcription in MK develop myelofibrosis. Since reduced RBC half-life subject these mice to continuous erythroid stress, we investigated the TPO/Mpl axis in this model. In Gata1low and wild-type mice, TPO mRNA was expressed by bone marrow (BM), spleen and liver. The greatest expression (by 300-fold) was detected in liver. Gata1low livers expressed TPO mRNA levels 6-fold greater than wild-type livers. TPO protein was detected in BM, spleen, liver and peritoneum washes and plasma. The greatest levels where detected in plasma. Gata1low plasma contained TPO levels 2-fold lower than wild-type plasma, but 2-times greater than plasma from bleed wild-type mice and Mplnull mice with similar thrombocytopenia, suggesting that TPO is overproduced in Gata1low mice. JAK2 and STAT5 were easily detected in Gata1low BM bur barely detectable in wild-type BM, suggesting that in the former MPL is prompt to signaling activation. Furthermore, Gata1low LSK expressed levels of Mpl mRNA 3-times greater than wild-type cells but expressed cell-surface levels of MPL 2-times lower than wild-type cells and similar to those on LSK from TPO-treated wild-type mice, suggesting that MPL is down-modulated in Gata1low LSK. The Crispinos hypothesis that in MF activation of TPO/MPL/JAK2 induces a ribosomal deficiency hampering GATA1 mRNA translation and the realization that this axis is activated in Gata1low mice made us question the original hypothesis that reduced content of GATA1 in Gata1low MK results from deletion of lineage-specific enhancers. Microarray analyses indeed identified that Gata1low BM express a discordant ribosome signature including reduced expression of RPS24 and RPS36A, two genes mutated in Diamond Blackfan Anemia, a disease characterized by inefficient GATA1 mRNA translation. Electron microscopy identified that the cytoplasm of Gata1low MK contained poorly developed endoplasmic reticulum with rare polysomes. In conclusion, these results validate the Gata1low model as a MF model by indicating that these mice express an activated TPO/MPL axis and an abnormal ribosomal signature which may reduce efficiency of Gata1 mRNA translation.
Publication Title
The thrombopoietin/MPL axis is activated in the Gata1<sup>low</sup> mouse model of myelofibrosis and is associated with a defective RPS14 signature.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A rare complication of multiple myeloma is a secondary extramedullary involvement, and the skin is one of the possible sites, due to the physiological homing of plasma cells (PCs) into the skin. The article reports a case of a relapsed refractory MM patient, who developed a cutaneous localization after 16 months from the diagnosis under Bortezomib treatment without a leukemic phase. Patient was refractory to Bortezomib. We analyzed the gene expression profiles, the immunophenotypic and immunohistochemistry profiles of MM cells across the course of the disease at the bone marrow and skin localization. Data obtained were further expanded by an immunohistochemistry analysis on selected molecules in a large cohort of MM patients with cutaneous localization. In particular we focused on the expression of chemokines and chemokine receptors involved in the PC skin homing.
Publication Title
Cutaneous localization in multiple myeloma in the context of bortezomib-based treatment: how do myeloma cells escape from the bone marrow to the skin?
Sample Metadata Fields
Sex, Age, Specimen part, Subject, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The first site exhibiting hematopoietic activity in mammalian development is the yolk sac blood island, which originates from the hemangioblast. Here we performed differentiation assays, as well as genome-wide molecular and functional studies in BL-CFCs to gain insight into the function of the essential Ldb1 factor in early primitive hematopoietic development. We show that the previously reported lack of yolk sac hematopoiesis and vascular development in Ldb1-/- mouse result from a decreased number of hemangioblasts and a block in their ability to differentiate into erythroid and endothelial progenitor cells. Transcriptome analysis and correlation with the genome wide binding pattern of Ldb1 in hemangioblasts revealed a number of direct target genes and pathways misregulated in the absence of Ldb1. The regulation of essential developmental factors by Ldb1 defines it as an upstream transcriptional regulator of hematopoietic/endothelial development. We show the complex interplay that exists between transcription factors and signaling pathways during the very early stages of hematopoietic/endothelial development and the specific signalling occurring in hemangioblasts in contrast to more advanced hematopoietic developmental stages. Finally, by revealing novel genes and pathways, not previously associated with early development, our study provides novel candidate targets to manipulate the differentiation of hematopoietic and/or endothelial cells.
Publication Title
Genome-wide analysis shows that Ldb1 controls essential hematopoietic genes/pathways in mouse early development and reveals novel players in hematopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Although a considerable number of reports indicate an involvement of the Hox-A10 gene in the molecular control of hematopoiesis, the conclusions of such studies are quite controversial since they support, in some cases, a role in the stimulation of stem cell self-renewal and myeloid progenitor expansion while, in others, implicate this transcription factor in the induction of monocyte - macrophage differentiation. To clarify this issue we analyzed the biological effects and the transcriptome changes determined in human primary CD34+ hematopoietic progenitors by retroviral transduction of a full length Hox-A10 cDNA. The results obtained clearly indicated that this homeogene is an inducer of monocyte differentiation, at least partly acting through the up-regulation of MafB gene, recently identified as master regulator of such maturation pathway. By using a combined approach based on computational analysis, EMSA experiments and luciferase assays, we were able to demonstrate the presence of a Hox-A10 binding site in the promoter region of the MafB gene, which suggested the likely molecular mechanism underlying the observed effect. Interestingly, stimulation of the same cells with the Vitamin D3 monocyte differentiation inducer resulted in a clear increase of Hox-A10 and MafB transcripts, indicating the existence of a precise transactivation cascade involving VDR, Hox-A10 and MafB transcription factors. Altogether these data allow to conclude that the Vitamin D3 / Hox-A10 pathway supports MafB function during the induction of monocyte differentiation.
Publication Title
The vitamin D3/Hox-A10 pathway supports MafB function during the monocyte differentiation of human CD34+ hemopoietic progenitors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The involvement of osteocytes in multiple myeloma (MM)-induced osteoclast formation and the occurrence of bone lesions are still unknown. Osteocytes regulate bone remodeling at least in part through the cell death and apoptosis triggering osteoclast recruitment and formation. In this study, firstly we shown that MM cells increased osteocyte death and affect their transcriptional profile evaluated by microarray analysis up-regulating osteoclastogenic cytokines as interleukin (IL)-11. Consistently we show that the conditioned media of human pre-osteocytes co-cultured with MM cells significantly increased osteoclastogenesis. To translate into a clinical perspective such in vitro evidences, we then performed histological analysis on bone biopsies obtained from MM patients, MGUS and healthy controls. We found a significant reduction in the number of viable osteocytes in MM patients as compared to controls. A significant negative correlation between the number of viable osteocytes and that of osteoclasts was also demonstrated. Moreover, as regards the skeletal involvement, we found that MM patients with bone lesions have a significant lower number of viable osteocyte than those without. Overall, our data suggest a role of osteocytic cell death in MM-induced osteoclast formation in vitro and MM bone disease in vivo in MM patients.
Publication Title
Increased osteocyte death in multiple myeloma patients: role in myeloma-induced osteoclast formation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples