Jak2 Deficiency Defines an EssentialDevelopmental Checkpoint in DefinitiveHematopoiesis

  title={Jak2 Deficiency Defines an EssentialDevelopmental Checkpoint in DefinitiveHematopoiesis},
  author={Hans J Neubauer and Ana Cumano and Mathias M{\"u}ller and Hong Wu and Ulrike Huffstadt and Klaus Pfeffer},

Figures and Tables from this paper

Critical Role of Jak2 in the Maintenance and Function of Adult Hematopoietic Stem Cells
Gene expression analysis reveals significant downregulation of genes related to HSC quiescence and self‐renewal in Jak2‐deficient LSK cells, and suggests that Jak2 plays a critical role in the maintenance and function of adult HSCs.
SOCS3 Is Essential in the Regulation of Fetal Liver Erythropoiesis
Erythropoiesis in the absence of janus-kinase 2: BCR-ABL induces red cell formation in JAK2(-/-) hematopoietic progenitors.
This study shows that certain signaling pathways activated by BCR-ABL segments distinct from its tyrosine kinase domain are essential for rescue of erythropoiesis in JAK2(-/-) progenitors.
Stat5 activation enables erythropoiesis in the absence of EpoR and Jak2.
Erythropoiesis requires erythropoietin (Epo) and stem cell factor (SCF) signaling via their receptors EpoR and c-Kit. EpoR, like many other receptors involved in hematopoiesis, acts via the kinase
Attenuated signaling by a phosphotyrosine-null Epo receptor form in primary erythroid progenitor cells.
The function of this JAK2-coupled but minimal PY-null EpoR-HM form appears to be attenuated in several contexts and to be assisted in vivo by compensatory mechanisms.
Genetic studies reveal an unexpected negative regulatory role for Jak2 in thrombopoiesis.
It is demonstrated that Jak2 in terminal megakaryopoiesis is not required for PLT production, and that Jak 2 loss in PLTs and MKs results in non-autonomous expansion of stem/progenitors and of MKs and PLTs via dysregulated TPO turnover.
The role of jak2a in zebrafish hematopoiesis.
Zebrafish jak2a is involved in primitive hematopoiesis under normal and deregulated conditions.
The redundant role of JAK2 in regulating pancreatic β-cell mass
The cytoprotective effects of exogenous EPO in the pancreatic β-cells, as well as the new findings on the redundant role of JAK2 in β-cell expansion after high-fat feeding in mice are highlighted.
Jak2a regulates erythroid and myeloid hematopoiesis during zebrafish embryogenesis
The expression level of Jak2a, which is a homolog of mammalian jak2 in zebrafish, is examined by quantitative reverse transcriptase (RT)-PCR, and the peak of mRNA expression occurred at 3.75 hours post fertilization (hpf), indicating that Jak 2a plays an important role in erythropoiesis and myeloid hematopoiesi.


Defects in B Lymphocyte Maturation and T Lymphocyte Activation in Mice Lacking Jak3
Data demonstrate that Jak3 is critical for the progression of B cell development in the bone marrow and for the functional competence of mature T cells.
Developmental defects of lymphoid cells in Jak3 kinase-deficient mice.
Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders.
  • K. Yoshida, T. Taga, T. Kishimoto
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
Results indicate that gp130 plays a crucial role in myocardial development and hematopoiesis during embryogenesis and some gp130-/- embryos show anemia due to impaired development of erythroid lineage cells.
A JAK1/JAK2 chimera can sustain alpha and gamma interferon responses
It is shown that mutant gamma1A cells carry a defect in, and can also be complemented by, the beta-subunit of the IFN-gamma receptor, consistent with the hypothesis that the mutation in these cells affects JAK2-receptor association.
Thrombopoietin, the ligand for the Mpl receptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice.
It is proposed that ML can function as an early acting cytokine and stimulate the proliferation of cell cycle dormant progenitors by shortening their G0 period.
Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages.
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.
Stat1 associates with c-kit and is activated in response to stem cell factor.
It is suggested that Stat1 is a component of the SCF signal-transduction pathway and that activated Stat1 binds the m67 oligonucleotide, a high-affinity SIE promoter sequence.