Although anemia is common in Shwachman-Diamond syndrome (SDS), the underlying mechanism remains unclear. We asked whether SBDS, which is mutated in most SDS patients, is critical for erythroid development. We found that SBDS expression is high early during erythroid differentiation. Inhibition of SBDS in CD34+ hematopoietic stem cells and early progenitors (HSC/Ps) and K562 cells led to slow cell expansion during erythroid differentiation. Induction of erythroid differentiation resulted in markedly accelerated apoptosis in the knockdown cells; however, proliferation was only mildly reduced. The percentage of cells entering differentiation was not reduced.
The ribosome-related protein, SBDS, is critical for normal erythropoiesis.
Specimen part, Disease, Disease stage
View SamplesOverexpression of human progastrin (hGAS) in mice has been observed to increase colonic mucosa proliferation significantly,
Progastrin stimulates colonic cell proliferation via CCK2R- and β-arrestin-dependent suppression of BMP2.
Sex, Age, Specimen part
View SamplesThe gene expression of bone marrow Hdc-/- and WT (LSK, Lin-c-kit+Sca-1+) hematopoetic stem and progenitor cells were isolated from Hdc-/- or WT mice. Cells were sorted by the cell surface markers of LSK total RNA was isolated from sorted 2,000 HSPCs using the ARCTURUS PicoPure RNA isolation kit (Life Technologies). cDNA was amplified and libraries were constructed by using the SMARTer Ultra Low Input RNA kit (Clontech Laboratories) and the Nextera XT DNA Library Preparation kit (Illumina) according to the respective manufacturer's instructions. Sequencing was performed on the Illumina HiSeq2500 platform. Overall design: a. Hdc-/- bone marrow HSPC (n=4) b. WT bone marrow HSPC (n=4)
Histidine decarboxylase (HDC)-expressing granulocytic myeloid cells induce and recruit Foxp3<sup>+</sup> regulatory T cells in murine colon cancer.
Specimen part, Subject
View SamplesBone marrow Hdc-GFP+/hi and Hdc-GFP-/loCD11b+Gr1+ cells were isolated from bones from histidine decarboxylase (Hdc) green fluorescent protein (Hdc-GFP) mice Hdc-GFP+/hiCD11b+Gr1+ cells and Hdc-GFP-/loCD11b+Gr1+ cells were sorted by combinations of GFP and myeloid cell surface markers CD11b and Gr1 and their differential mRNA expression compared with Affymetrix microarrays.
Histidine decarboxylase (HDC)-expressing granulocytic myeloid cells induce and recruit Foxp3<sup>+</sup> regulatory T cells in murine colon cancer.
Sex, Specimen part
View SamplesInterleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which regulates plasma cell differentiation and T cell homeostasis. We identified an IL-21 response element downstream of Prdm1 that binds the transcription factors STAT3 and IRF4, which are required for optimal Prdm1 expression. Genome-wide ChIP-Seq mapping of STAT3- and IRF4-binding sites showed that most regions with IL-21-induced STAT3 binding also bound IRF4 in vivo, and furthermore, revealed that the noncanonical TTCnnnTAA GAS motif critical in Prdm1 was broadly used for STAT3 binding. Comparing genome-wide expression array data to binding sites revealed that most IL-21-regulated genes were associated with combined STAT3-IRF4 sites rather than pure STAT3 sites. Correspondingly, ChIP-Seq analysis of Irf4_/_ T cells showed greatly diminished STAT3 binding after IL-21 treatment, and Irf4_/_ mice showed impaired IL- 21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4.
Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 transcription factors.
Specimen part
View SamplesThe gene expression of murine splenic myeloid derived suppressor cells treated with Tff2 is characterized. The motivation of the study originates in the fact that Gr1+Cd11b+ myeloid-derived suppressor cells (MDSCs), which resemble immature myeloid cells (IMCs), expand during cancer in response to inflammatory cytokines and accumulate in the spleen. MDSCs promote neoplastic progression through their suppression of anti-tumourigenic cytotoxic T-cells. MDSCs are also rapidly expanded following acute insults, but in cancer as opposed to acute inflammation, MDSCs persist. It is now recognized that a vagally-mediated, anti-inflammatory reflex arc promoting acetylcholine secretion by Cd4+ (Cd44hiSelllo) T cells, is necessary for a return to homeostasis after an acute insult. Failure of this restorative neural circuit might contribute to unabated procarcinogenic inflammation, with the chronic expansion of MDSCs driving carcinogenesis. Trefoil factor 2 (Tff2) is a secreted anti-inflammatory peptide produced by both epithelial cells and a small subset of splenic T cell.
Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer.
Sex, Age, Specimen part
View SamplesIdentification of genetic polymorphisms associated with inter-individual variation in immune response to Mycobacterium tuberculosis infection.
Deciphering the genetic architecture of variation in the immune response to Mycobacterium tuberculosis infection.
Sex
View SamplesDclk1 (Doublecortin like kinase-1) labels a rare population of long-lived and largely quiescent cells in the adult mouse pancreas. The expression of Dclk1+ vs Dclk1- pancreatic cells (mostly acinar) is observed. Overall design: Dclk1+ vs Dclk1-
Dclk1 Defines Quiescent Pancreatic Progenitors that Promote Injury-Induced Regeneration and Tumorigenesis.
Specimen part, Cell line, Subject
View SamplesDifferential expression of Hdc-GFPhi HSPC VS Hdc-GFPlo HSPC hematopoetic stem and progenitor cells from mouse bone marrow Overall design: Bone marrow Hdc-GFPhi and Hdc-GFPlo HSPC (LSK, Lin-c-kit+Sca-1+) hematopoetic stem and progenitor cells were isolated from femur, tibia, illium, and vertebra bones of histidine decarboxylase (Hdc) green fluorescent protein (Hdc-GFP) mice Hdc-GFPhi HSPC and Hdc-GFPlo HSPC cells were sorted by combinations of GFP and the cell surface markers of LSK, total RNA was isolated from sorted 2,000 HSPCs using ARCTURUS PicoPure RNA isolation kit (Life Technologies). cDNA was amplified and libraries were constructed by using the SMARTer Ultra Low Input RNA kit (Clontech Laboratories) and the Nextera XT DNA Library Preparation kit (Illumina) according to the respective manufacturer's instructions. Sequencing was performed on the Illumina HiSeq 2500 platform. a. Hdc-GFPhi bone marrow HSPC cells (n=4) b. Hdc-GFPlo bone marrow HSPC cells (n=4)
Bone Marrow Myeloid Cells Regulate Myeloid-Biased Hematopoietic Stem Cells via a Histamine-Dependent Feedback Loop.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Specimen part, Cell line
View Samples