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Journal ArticleDOI

Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages

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TLDR
The developmental programs of lymphoid and myeloid lineages require a common genetic function likely acting at the level of a multipotential progenitor, and mice carrying a mutation in the PU.1 locus were generated by gene targeting.
Abstract
The transcription factor PU.1 is a hematopoietic-specific member of the ets family. Mice carrying a mutation in the PU.1 locus were generated by gene targeting. Homozygous mutant embryos died at a late gestational stage. Mutant embryos produced normal numbers of megakaryocytes and erythroid progenitors, but some showed an impairment of erythroblast maturation. An invariant consequence of the mutation was a multilineage defect in the generation of progenitors for B and T lymphocytes, monocytes, and granulocytes. Thus, the developmental programs of lymphoid and myeloid lineages require a common genetic function likely acting at the level of a multipotential progenitor.

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Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1

TL;DR: It is shown that the chemokine PBSF/SDF-1 has several essential functions in development, including B-cell lymphopoiesis and bone-marrow myelopoiedis and a cardiac ventricular septal defect.
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AML1, the Target of Multiple Chromosomal Translocations in Human Leukemia, Is Essential for Normal Fetal Liver Hematopoiesis

TL;DR: The results suggest that AML1-regulated target genes are essential for definitive hematopoiesis of all lineages, and that this defect was intrinsic to the stem cells in that AMl1-/-ES cells failed to contribute to hematocerosis in chimeric animals.
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Definitive Hematopoiesis Is Autonomously Initiated by the AGM Region

TL;DR: A novel in vitro organ culture system is presented demonstrating that, at day 10 in gestation, hematopoietic stem cells initiate autonomously and exclusively within the aorta-gonad-mesonephros (AGM) region, suggesting that the AGM region is the source of the definitive adult hematosynthesis system, which subsequently colonizes the liver.
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B cell development pathways.

TL;DR: Progress in understanding some aspects of this process in the mouse bone marrow is reviewed, focusing on delineation of the earliest stages of commitment, on pre-B cell receptor selection, and B cell tolerance during the immature-to-mature B cell transition.
Journal ArticleDOI

Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities.

TL;DR: While the PU.1 protein appears not to be essential for myeloid and lymphoid lineage commitment, it is absolutely required for the normal differentiation of B cells and macrophages.
References
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Journal ArticleDOI

RAG-1-deficient mice have no mature B and T lymphocytes

TL;DR: The introduction of a mutation in RAG-1 into the germline of mice via gene targeting in embryonic stem cells is described and it is shown that this mutation either activates or catalyzes the V(D)J recombination reaction of immunoglobulin and T cell receptor genes.
Journal ArticleDOI

RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement

TL;DR: Loss of RAG-2 function in vivo results in total inability to initiate V(D)J rearrangement, leading to a novel severe combined immune deficient (SCID) phenotype.
Journal ArticleDOI

Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes

TL;DR: A positive and negative selection procedure is described that enriches 2,000-fold for those cells that contain a targeted mutation in mouse embryo-derived stem cells.
Journal ArticleDOI

Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow.

TL;DR: Functional analysis demonstrates that the proliferative response to IL-7, an early B lineage growth factor, is restricted to S7+ stages and, furthermore, that an additional, cell contact-mediated signal is essential for survival of Fr.
Book

Teratocarcinomas and embryonic stem cells : a practical approach

TL;DR: The results allowed us to assess the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals, not necessarily belonging to the same breeds.
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