Project description:Compared gene expression between Lin-Sca1-cKit+ myeloid progenitors isolated from the bone marrow of 6-8 week old wildtype and Mirc11-/- mice. Previously observed that overexpression of Mirc11 in hematopoietic progenitors increased myeloid differentiation whereas loss of Mirc11 decreased myeloid differentiation. Performed RNA-seq to identify potential genes involved in myeloid differentiation regulated by Mirc11. Gene expression analysis of Mirc11 deficient myeloid progenitors revealed a decrease in Toll like receptor and interferon signaling. This anti-inflammatory phenotype was further observed in mature cells as Mirc11-/- bone marrow derived macrophages (BMDMs) have an attenuated response to inflammatory lip-opolysaccharide (LPS).
Project description:The role of the INV16 genetic translocation in acute myeloid leukemia may be to alter expression in primitive hematopoietic progenitors of genes important for regulating hematopoiesis. To identify transcriptional targets of INV16 in primitive hematopoietic progenitors, FACS-purified progenitors from murine bone marrow were transduced with retrovirus encoding INV16 and analyzed for alterations in gene expression using whole transcriptome expression arrays.
Project description:Aim of the experiment was to compare the genes enriched in the heavy polysome fraction of myeloid progenitors originating from control Elp3fl/fl mice, and in myeloid progenitors originating from mice that underwent hematopoietic cell-restricted deletion of the catalytic subunit Elp3 of the Elongator complex (Elp3HscKO mice). The Elp3fl/fl strain was generated in house and first described in (DOI: 10.1084/jem.20142288). Littermates of 8-12 weeks old were used in all experiments.
Project description:The role of the INV16 genetic translocation in acute myeloid leukemia may be to alter expression in primitive hematopoietic progenitors of genes important for regulating hematopoiesis. To identify transcriptional targets of INV16 in primitive hematopoietic progenitors, FACS-purified progenitors from murine bone marrow were transduced with retrovirus encoding INV16 and analyzed for alterations in gene expression using whole transcriptome expression arrays. Normal murine bone marrow cells of the Lineage-negative, c-Kit+, Sca-1+, Flt3-negative phenotype (KSLF) were FACS-purified, transduced with retrovirus encoding INV16 (INV), the non-leukemogenic INV16 mutant deleted of the assembly competent domain (ACD) or empty retroviral vector control (MIB). Productively transduced, GFP-positive cells were FACS-sorted 24 hours later, and RNA isolated and analyzed using Affymetrix whole transcriptome expression arrays. Replicate numbers of sorts/transductions/analyses of 4, 3, and 5 were performed for INV, ACD, and MIB, respectively.
Project description:Recent studies have documented genome-wide binding patterns of transcriptional regulators and their associated epigenetic marks in hematopoietic cell lineages. In order to determine how epigenetic marks are established and maintained during developmental progression, we have generated long-term cultures of hematopoietic progenitors by enforcing the expression of the E-protein antagonist Id2. Hematopoietic progenitors that express Id2 are multipotent and readily differentiate upon withdrawal of Id2 expression into committed B lineage cells, thus indicating a causative role for E2A (Tcf3) in promoting the B cell fate. Genome-wide analyses revealed that a substantial fraction of lymphoid and myeloid enhancers are premarked by the poised or active enhancer mark H3K4me1 in multipotent progenitors. Thus, in hematopoietic progenitors, multilineage priming of enhancer elements precedes commitment to the lymphoid or myeloid cell lineages. This SuperSeries is composed of the SubSeries listed below.
Project description:Collombet2016 - Lymphoid and myeloid cell
specification and transdifferentiation
This model is described in the article:
Logical modeling of lymphoid
and myeloid cell specification and transdifferentiation
Samuel Collombet, Chris van Oevelen,
Jose Luis Sardina Ortega, Wassim Abou-Jaoudé, Bruno Di
Stefano, Morgane Thomas-Chollier, Thomas Graf, and Denis
Thieffry
Proceedings of the National Academy of
Sciences of the United States of America
Abstract:
Blood cells are derived from a common set of hematopoietic
stem cells, which differentiate into more specific progenitors
of the myeloid and lymphoid lineages, ultimately leading to
differentiated cells. This developmental process is controlled
by a complex regulatory network involving cytokines and their
receptors, transcription factors, and chromatin remodelers.
Using public data and data from our own molecular genetic
experiments (quantitative PCR, Western blot, EMSA) or
genome-wide assays (RNA-sequencing, ChIP-sequencing), we have
assembled a comprehensive regulatory network encompassing the
main transcription factors and signaling components involved in
myeloid and lymphoid development. Focusing on B-cell and
macrophage development, we defined a qualitative dynamical
model recapitulating cytokine-induced differentiation of common
progenitors, the effect of various reported gene knockdowns,
and the reprogramming of pre-B cells into macrophages induced
by the ectopic expression of specific transcription factors.
The resulting network model can be used as a template for the
integration of new hematopoietic differentiation and
transdifferentiation data to foster our understanding of
lymphoid/myeloid cell-fate decisions.
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MODEL1610240000.
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