Paracrine stimulation effect of human salispheres on mouse salivary gland
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ABSTRACT:
PROVIDER: PRJNA295221 | ENA |
REPOSITORIES: ENA
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Project description:Paracrine stimulation effect of autologous salispheres on mouse salivary gland
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Project description:Human salispheres, a culture of stem/progenitor cells, represent a potential therapy for radiation induced hyposalivation. Radiation-induced hyposalivation dramatically reduces quality of life of patients. We have demonstrated the potential of human salispheres to engraft and differentiate when transplanted into a mouse model of hyposalivation, in the manuscript associated with these data. We also demonstrate the functional recovery of irradiated salivary glands (SGs) following human salisphere transplantation, by the measurement of saliva production. We previously employed Illumina microarrays to determine if transplanted human salisphere cells exert a paracrine stimulatory effect on recipient mouse SGs. Results of this array unveiled a large cohort of immuneresponse genes unregulated following human salisphere transplantation. In order to negate this immune response and unveil any true paracrein stimulatory effects, we performed autologous transplantation of salispheres from NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice, the same model employed in our first microarray study, in the irradiated SGs of NSG mice. 6 samples were analysed in total. Total RNA from 3 irradiated control SGs (5Gy irradiation) and 3 salivary glands transplanted with 100,000 NSG salispheres.
2015-09-10 | E-GEOD-72870 | biostudies-arrayexpress
Project description:Human salispheres, a culture of stem/progenitor cells, represent a potential therapy for radiation induced hyposalivation. Radiation-induced hyposalivation dramatically reduces quality of life of patients. We have demonstrated the potential of human salispheres to engraft and differentiate when transplanted into a mouse model of hyposalivation, in the manuscript associated with these data. We also demonstrate the functional recovery of irradiated salivary glands (SGs) following human salisphere transplantation, by the measurement of saliva production. When analyzing human salisphere- transplanted SGs for the presence of human cells, we noted that the highest proportion of human cells were present 1 week after transplantation. This microarray study was designed to determine if paracrine signaling from transplanted human salisphere cells to recipient mouse SGs accounts for a part of the functional recovery of the recipient SG we observe. We compare the transcriptome from irradiated control SG of immunecompromised NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice with that of NSG SGs transplanted with 100,000 human salisphere cells. All mice were sacrificed 1 week following transplantation (or non-transplantation in case of controls) and Illumina array chips used to detect differences in gene expression. 6 samples were analysed in total. Total RNA from 3 irradiated control SGs (5Gy irradiation) and 3 salivary glands transplanted with 100,000 human salispheres.
2015-09-10 | E-GEOD-72869 | biostudies-arrayexpress
Project description:Human salispheres, a culture of stem/progenitor cells, represent a potential therapy for radiation induced hyposalivation. Radiation-induced hyposalivation dramatically reduces quality of life of patients. We have demonstrated the potential of human salispheres to engraft and differentiate when transplanted into a mouse model of hyposalivation, in the manuscript associated with these data. We also demonstrate the functional recovery of irradiated salivary glands (SGs) following human salisphere transplantation, by the measurement of saliva production. We previously employed Illumina microarrays to determine if transplanted human salisphere cells exert a paracrine stimulatory effect on recipient mouse SGs. Results of this array unveiled a large cohort of immuneresponse genes unregulated following human salisphere transplantation. In order to negate this immune response and unveil any true paracrein stimulatory effects, we performed autologous transplantation of salispheres from NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice, the same model employed in our first microarray study, in the irradiated SGs of NSG mice.
2015-09-10 | GSE72870 | GEO
Project description:Human salispheres, a culture of stem/progenitor cells, represent a potential therapy for radiation induced hyposalivation. Radiation-induced hyposalivation dramatically reduces quality of life of patients. We have demonstrated the potential of human salispheres to engraft and differentiate when transplanted into a mouse model of hyposalivation, in the manuscript associated with these data. We also demonstrate the functional recovery of irradiated salivary glands (SGs) following human salisphere transplantation, by the measurement of saliva production. When analyzing human salisphere- transplanted SGs for the presence of human cells, we noted that the highest proportion of human cells were present 1 week after transplantation. This microarray study was designed to determine if paracrine signaling from transplanted human salisphere cells to recipient mouse SGs accounts for a part of the functional recovery of the recipient SG we observe. We compare the transcriptome from irradiated control SG of immunecompromised NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice with that of NSG SGs transplanted with 100,000 human salisphere cells. All mice were sacrificed 1 week following transplantation (or non-transplantation in case of controls) and Illumina array chips used to detect differences in gene expression.
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Project description:Microarray analysis using the HumanHT-12 v4 Expression BeadChip was utilized to determine the biological function of IL-22. The data indicate an extensive effect of IL-22 on many major molecular functions including activation of antimicrobial genes and downregulation of immune-associated pathways. Functional studies performed in-vitro using human salivary gland cells treated with IL-22 indicated a direct effect of IL-22 on cell cycling, specifically reducing cellular proliferation at the G2-M phase by activation of STAT3. Total RNAs were obtained from salivary gland cells stimulated with recombinant IL-22 for 45 minutes. Differential expression analyses were conducted using the LIMMA package from the Bioconductor project. MTT assay, flow cytometry and western blotting were used to identify the function of IL-22 on human salivary gland cells.
2015-10-27 | E-GEOD-74389 | biostudies-arrayexpress
Project description:Salivary gland hypofunction is a common adverse effect during and after radiotherapy of head and neck cancers, resulting in the dry mouth syndrome called xerostomia. Previous studies suggested that the functionality of the salivary gland is under the regulation of the circadian clock, however, the extent and scope of this regulation remains unexplored. Here, we profiled the diurnal fluctuation of gene expression in the mouse submandibular salivary gland. We further analyzed the regulatory role of key circadian transcription factors Bmal1, Nr1d1 (Rev-erba), and Dbp, which revealed a wide range of potential down-stream target genes. The circadian clock was disrupted upon irradiation, as revealed by gene expression analysis. We propose that the mechanism of salivary gland hypofunction in radiotherapy involves perturbation of the circadian clock.
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Project description:Loss of Irf6 leads to disruption of branching morphogenesis and secretory acnii formation in salivary gland. To determine the differentially expressed genes in Irf6 mutant, embryonic salivary gland tissues were extracted at E14.5.
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