ABSTRACT: Transcription profiling by array of bone marrow cells from wild type, Fancc-deficient, Fancg-deficient, and doubly deficient (Fancc/Fancg) mice
Project description:To identify factors that could explain why mice transplanted with Vim deficient bone marrow display decreased atherosclerosis despite increased inflammation, we performed global gene expression profiling of bone-marrow derived macrophages from vimentin-deficient or wild-type littermates on C57BL/6 background.
Project description:To identify factors that could explain why mice transplanted with Vim deficient bone marrow display decreased atherosclerosis despite increased inflammation, we performed global gene expression profiling of bone-marrow derived macrophages from vimentin-deficient or wild-type littermates on C57BL/6 background. We elucidated the role of vimentin in atherogenic low-density receptorâ deficient mice after bone marrow transplantation from vimentin-deficient mice.
Project description:<p>We are studying the natural history, pathogenesis and treatment of patients with WHIM syndrome, an immunodeficiency disorder characterized by warts, hypogammaglobulinemia, recurrent infections and neutropenia usually due to autosomal dominant gain-of-function mutations in chemokine receptor <i>CXCR4</i>. We have identified a patient born with WHIM syndrome and the WHIM mutation <i>CXCR4<sup>R334X</sup></i> who has been disease-free for 20 years and who lacks <i>CXCR4<sup>R334X</sup></i> in myeloid cells, the cells that drive disease manifestations. She is a genetic and hematopoietic mosaic, since she still has the mutation in lymphoid cells and non-hematopoietic cells. Cytogenetics and microarray analysis revealed that the mechanism of loss of the mutation was deletion of the mutant allele from one copy of chromosome 2. Whole genome sequencing of patient neutrophil and skin fibroblast genomic DNA revealed that the mechanism of deletion was chromothripsis, a process of chromosome shattering resulting in deletions and rearrangements of the non-deleted chromosomal segments. In the patient, this process evidently occurred in a single hematopoietic stem cell (HSC), resulting in deletion of the disease allele <i>CXCR4<sup>R334X</sup></i> and one copy of 163 other genes on chromosome 2. This HSC evidently acquired a growth advantage and repopulated the HSC population and the myeloid lineage. Consistent with this, studies using gene targeted mice in competitive bone marrow transplantation experiments revealed that selective <i>Cxcr4</i> haploinsufficiency (inactivation of one copy of <i>Cxcr4</i> and not of any other genes) was sufficient to confer a strong engraftment advantage over bone marrow cells from wild type mice as well as bone marrow cells from a mouse model of WHIM syndrome. These results suggest that <i>CXCR4</i> knockdown may be a useful strategy to enhance bone marrow engraftment in the absence of toxic bone marrow conditioning regimens.</p>
Project description:To investigate the role of hematopoietic Tet2 loss on the development of steatohepatitis, mice were transplanted with wild type or Tet2 deficient bone marrow cells and fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Gene expression profiling analysis of sorted liver macrophages was performed.
Project description:To investigate the role of hematopoietic Tet2 loss on the development of steatohepatitis, mice were transplanted with wild type or Tet2 deficient bone marrow cells and fed a choline-deficient, L-amino acid-defined, high-fat diet. Gene expression profiling analysis of bulk liver RNA was then performed.
Project description:We isolated RNA from sorted common myeloid progenitor cells from wild-type fetal liver, wild-type adult bone marrow, transgenic Lin28b bone marrow, let-7b/c knock-out bone marrow, and Lin28b-deficient fetal liver and compared mRNA expression profiles.
Project description:Transcriptional profiling of calpain-6-deficient murine bone marrow-derived macrophages comparing with calpain-6 wild-type macrophages. Total RNA was extracted from the pooled cells.
Project description:Transcriptional profiling of calpain-6-deficient murine bone marrow-derived macrophages comparing with calpain-6 wild-type macrophages. Total RNA was extracted from the pooled cells. Two-condition experiment, wild-type macrophages vs. calpain-6-deficiennt macrophages. The cells were derived from four mice, and were pooled for analysis.
Project description:By performing RNA-seq analysis on bone marrow neutrophils from the Alkbh5-deficient mice and Wild-type littermates undergoing CLP-induced sepsis, we want to investigate the effect of ALKBH5 on transcriptional landscape of mouse bone marrow neutrophils during bacterial infection. Then, we performed gene expression profiling and Gene Ontology enrichment analysis of the significantly differentially expressed genes using data obtained from RNA-seq.