Project description:The capacity of the hematopoietic system to promptly respond to peripheral demands relies on adequate pools of progenitors able to transiently proliferate and differentiate in a regulated manner. However, little is known about factors that may restrain progenitor maturation to maintain their reservoirs. In addition to a profound defect in hematopoietic stem cell (HSC) self-renewal, conditional knockout mice for the Pbx1 proto-oncogene have a significant reduction in lineage-restricted progenitors, including common myeloid progenitors (CMPs) and, to a lesser extent, granulocyte-monocyte progenitors (GMPs). Through analysis of purified progenitor proliferation, differentiation capacity and transcriptional profiling, we demonstrate that in the absence of Pbx1 the CMP pool is reduced due to aberrantly rapid myeloid maturation, associated with decreased expression of Meis1 and its targets including Flt3. BM cells were obtained from multiple bones of individual three to five week old Tie2Cre+.Pbx1-/f or Tie2Cre+.Pbx1+/f control mice (4-5 biological replicates/group). CMPs and GMPs were sorted by flow cytometry according to the following markers: Lin-/c-Kit+/Sca-/CD34+/CD16/32int, and Lin-/c-Kit+/Sca-/CD34+/CD16/32high, respectively, prior to RNA extraction.
Project description:Through gene expression analysis of CMPs and GMPs at single cell levels, we identified CD62L as a marker to reveal the heterogeneity of CMPs and GMPs. We confirmed that the CD62L-low CMPs represent ‘bona fide’ CMPs, whereas CD62L-high CMPs are mostly restricted to GMP potentials both in mice and humans. In addition, we identified CD62L-neg GMPs as the most immature subsets in GMPs and Ly6c+CD62L-low and Ly6c+CD62L-high GMPs are skewed to neutrophil and monocyte differentiation, respectively. We performed gene expression profiling of CD62L-low CMPs, CD62L-high CMPs, CD62L-neg GMPs, CD62L-low GMPs, CD62L-high GMPs, bulk CMPs, and bulk GMPs.
Project description:Transcriptional changes occurring in the CMPs and GMPs of untreated "CMP pattern" and "GMP pattern" MDS patients were compared with the transcriptional profile of CMPs and GMPs from healthy donors
Project description:The capacity of the hematopoietic system to promptly respond to peripheral demands relies on adequate pools of progenitors able to transiently proliferate and differentiate in a regulated manner. However, little is known about factors that may restrain progenitor maturation to maintain their reservoirs. In addition to a profound defect in hematopoietic stem cell (HSC) self-renewal, conditional knockout mice for the Pbx1 proto-oncogene have a significant reduction in lineage-restricted progenitors, including common myeloid progenitors (CMPs) and, to a lesser extent, granulocyte-monocyte progenitors (GMPs). Through analysis of purified progenitor proliferation, differentiation capacity and transcriptional profiling, we demonstrate that in the absence of Pbx1 the CMP pool is reduced due to aberrantly rapid myeloid maturation, associated with decreased expression of Meis1 and its targets including Flt3.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:We have sequenced using single end and paired end sequencing GMPs, CMPs, EoPs, SiglecF+IL5ra- GMPs and eosinophils to be able to characterise this new subset of GMPs and to be able to give it some context within a lineage trajectory analysis
Project description:We created mice, which are deficient for Myc specifically in cardiac myocytes by crossing crossed Myc-floxed mice (Mycfl/fl) and MLC-2VCre/+ mice. Serial analysis of earlier stages of gestation revealed that Myc-deficient mice died prematurely at E13.5-14.5. Morphological analyses of E13.5 Myc-null embryos showed normal ventricular size and structure; however, decreased cardiac myocyte proliferation and increased apoptosis was observed. BrdU incorporation rates were also decreased significantly in Myc-null myocardium. Myc-null mice displayed a 3.67-fold increase in apoptotic cardiomyocytes by TUNEL assay. We examined global gene expression using oligonucleotide microarrays. Numerous genes involved in mitochondrial death pathways were dysregulated including Bnip3L and Birc2. Keywords: wildtype vs Myc-null