Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA148343 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Retroviral transduction of Pax5-deficient pro/preB cell lines with a doxycycline-inducible (TetON) form of the human Pax5 (huPax5) gene yielded cell clones which could be induced to different levels of huPax5 expression. Clones inducible to high levels developed B220+/CD19/+IgM+ B cells, while clones with low levels differentiated to B220+/CD19- /CD11b+/Gr-1- B-lymphoid/myeloid “bi-phenotypic” cells in vitro and in vivo. “Bi-phenotypic” cells could also be developed from high level-inducible cells by lower concentrations of doxycycline, inducing lower levels of huPax5 in vitro. Microarray analyses of genes expressed at these lower levels of huPax5 identified C/ebpα, C/ebpδ, Pu.1, Csf1r, Csf2r and Gata-3 as myeloid-related genes selectively expressed in the pro/preB cells which can develop under myeloid/lymphoid conditions to “bi-phenotypic” cells. Therefore, reduced expression of huPax5 during the induction of early lymphoid progenitors to B-lineage-committed cells can fix this cellular development at a stage that has previously been seen during embryonic development and in ALL-like “bi-phenotypic” acute leukemias (BAL).
2012-08-14 | GSE33875 | GEO
Project description:PAx5 is indispensible for the committment if early lymphoid progenitors to the B cell lineage as well as for the development and maintenance of B cells. To better understand the functional importance of Pax5 in the later stages of B cell development and investigate the targets of Pax5 regulation, we established a novel Pax5 deficient DT40 B cell line.
2005-04-17 | E-MEXP-270 | biostudies-arrayexpress
Project description:Array analysis of My-bi and Ly-bi HSC identifies candidate molecules for myeloid-bias. Collectively the data show that HSC in adults are largely epigenetically fixed in differentiation and self-renewal behavior. A direct examination of the epigenetic mechanisms that imprint HSC is difficult. However, an indirect way of assessing the effects of epigenetic imprinting is to look for the expressed gene programs of different types of HSC. Therefore, we performed an array analysis in collaboration with Dr. Michael Cooke. My-bi and Ly-bi HSC were identified in clonally repopulated hosts. The analysis returned 218 differentially expressed genes (M-bM-^IM-% Log2 M-bM-^IM-%2, p< 0.05) of which 36 were found to be overexpressed in My-bi HSC and the rest was overexpressed in Ly-bi HSC (Appendix A). There was no difference in expression levels for genes known to be involved in fate decisions during differentiation. This agrees well with our data that lineage bias is a stable function of a HSC, and does not reflect a differentiated type of cell. Gene expression profiles of myeloid-biased (My-bi) and lymphoid-biased (Ly-bi) stem cells were analyzed. Clonally repopulated hosts were generated by limiting dilution of bone marrow into ablated hosts and lineage bias was determined. Single My-bi (Tenor) and Ly-bi (Mort) repopulated hosts were sacrificed and Donor type HSC were enriched for Sca-1+, Lin- cells. Two technical replicates of RNA extract were run from each clone.
2013-05-01 | E-GEOD-41702 | biostudies-arrayexpress
Project description:Investigation of immune cell differentiation and function is limited by shortcomings of suitable and scalable experimental systems. Although forced expression of certain Hox genes allows immortalization of hematopoietic progenitor cells, their differentiation potential is limited to select myeloid lineages. Here we show that an estrogen-regulated form of Hoxb8 that is retrovirally delivered into bone marrow cells can be used along with FLT3 ligand to conditionally immortalize early hematopoietic progenitor cells (Hoxb8-FL). Hoxb8-FL cells have lost self-renewal capacity and the ability to adopt megakaryocyte/ erythroid lineage fates, but sustain myeloid and lymphoid differentiation potential. Hoxb8-FL cells differentiate in vitro and in vivo into different myeloid and lymphoid cell types, including macrophages, granulocytes, dendritic cells and B- and T-lymphocytes, which are phenotypically and functionally indistinguishable from their primary counterparts. Given the simplicity to generate Hoxb8-FL cells and their unlimited proliferative capacity, this system provides unique opportunities to investigate cell differentiation and immune cell functions. Hoxb8 expressing immortalized cells
2013-06-05 | E-GEOD-45759 | biostudies-arrayexpress
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.
This model is hosted on
BioModels Database
and identified by:
MODEL1610240000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-06-08 | MODEL1610240000 | BioModels
Project description:Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.
2005-08-16 | E-SMDB-3450 | biostudies-arrayexpress
Project description:IKKa, a major regulator of noncanonical and canonical NF-kB pathways, is essential for B-lymphocyte maturation and secondary lymph organ formation. No evidence of IKKa regulating early B cell development currently exists. Here we found reduced pre-pro-B and pro-B cells but increased myeloid-erythroid lineages in the bone marrow (BM) of knockin mice expressing reduced and kinase-dead IKKa (KA/KA). The KA/KA BM cells recaptured their defects in wild-type recipients and KA/KA fetal liver displayed reduced B cells but increased progenitors. IKKa inactivation impaired both NF-kB pathways and deregulated expression of many genes required for early B cell commitment and hematopoiesis, including downregulated Pax5, IRF4, and Ikaros expression, but increased C/EBPa, GATA1, and Stat3 levels. Reintroduced combined NF-kB components, Pax5, and IKKa promoted BM B cell differentiation and repressed myeloid-erythroid lineages. Our studies revealed a new function of IKKa in a coordinated development process of B-lineage and erythroid-myeloid lineages during hematopoiesis via multiple pathways. Microarray analysis was performed on RNA isolated from the BM of B220+ cells isolated from 4-week old WT and KA/KA mice using affymetrix mouse 430 2.0 array chip, containing 45,000 genes, at the Laboratory of Molecular Technology SAIC-Frederick. Data were normalized, and log2 transformations were generated using Partek software (St. Louis, MO, USA).
2011-07-02 | E-GEOD-30363 | biostudies-arrayexpress
Project description:The classical model of hematopoiesis posits the segregation of lymphoid and myeloid lineages as the earliest fate decision. The validity of this model has recently been questioned in the mouse, however little is known concerning lineage potential of human progenitors. Here we provide a comprehensive analysis of the human hematopoietic hierarchy by clonally mapping the developmental potential of 7 progenitor classes from neonatal cord blood and adult bone marrow. Human multi-lymphoid progenitors, identified as a distinct population of Thy1-/loCD45RA+ cells within the CD34+CD38- stem cell compartment, gave rise to all lymphoid cell types, as well as monocytes, macrophages, and dendritic cells, indicating that these myeloid lineages arise in early lymphoid lineage specification. Thus, as in the mouse, human hematopoiesis does not follow a rigid model of myeloid-lymphoid segregation. Total RNA was extracted from 5 - 10,000 sorted cord blood progenitor cells to compare gene expression
2010-06-23 | E-GEOD-21973 | biostudies-arrayexpress
Project description:Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly. 3 old mice and 5 young mice were assayed
2007-12-19 | E-GEOD-4332 | biostudies-arrayexpress
Project description:To examine the role of PAX5 alterations in leukemogenesis, we performed mutagenesis screens of mice heterozygous for a loss-of-function Pax5 allele. Both chemical and retroviral mutagenesis resulted in a significantly increased penetrance and reduced latency of leukemia, with a shift to B-lymphoid lineage. We observed a range of maturation of lymphoid tumors, and genomic profiling identified a high frequency of secondary genomic mutations, deletions and retroviral insertions targeting B-lymphoid development, including Pax5, and additional genes and pathways known to be mutated in ALL, including tumor suppressors, Ras and JAK-STAT signaling. These results support the notion that loss-of-function of PAX5 is a central event in leukemogenesis and contributes to the arrest in lymphoid maturation characteristic of this disease. Moreover, we validate the role of mutations in additional pathways and demonstrate that sequential acquisition of genetic alterations is required for establishment of leukemia.
2015-04-10 | GSE67611 | GEO