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.
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.
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.
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.
Project description:Salivary glands that produce and secret saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. The long-term maintenance of diverse salivary gland cells in organoids remains problematic. Here, we established long-term murine salivary gland organoids from 3 major salivary glands, including parotid gland (PG), submandibular gland (SMG), and sublingual gland (SLG). Murine salivary gland organoids expressed gland-specific genes and proteins of acinar, myoepithelial, and duct cells. Organoids were maintained in growth media (named GEM) and further underwent differentiation in differentiation media (named DAM). Our study will provide an experimental platform for the exploration of mechanisms involvled in tissue regeneration, development, or several salivary gland diseases.
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.
Project description:Ionizing radiation (IR) – induced salivary gland damage is a common adverse effect in radiotherapy for patients with head and neck cancers. Currently, there is no effective treatment for the resulting salivary gland hypofunction and xerostomia (dry mouth). Here we profiled the acute gene expression change in the mouse submandibular salivary gland, and defined its damage response patterns at the transcriptome level.
Project description:Salivary glands that produce and secret saliva, which is essential for lubrication, digestion, immunity, and oral homeostasis, consist of diverse cells. Maintenance of diverse salivary gland cells in organoids remains problematic. Here, we established human salivary gland organoids, which is composed of multiple cellular subsets, from 3 major salivary glands, including parotid gland (PG), submandibular gland (SMG), and sublingual gland (SLG). Human salivary gland organoids expressed gland-specific genes and proteins of acinar, myoepithelial, and duct cells. Organoids were maintained in growth media (named GEM) and further underwent differentiation in differentiation media (named DAM). Our study will provide an experimental platform for the exploration of mechanisms involvled in tissue regeneration, development, or several salivary gland diseases.