scholarly journals Elevated Nuclear Factor Erythroid-2 Levels Promote Epo-Independent Erythroid Maturation and Recapitulate the Hematopoietic Stem Cell and Common Myeloid Progenitor Expansion Observed in Polycythemia Vera Patients

2013 ◽  
Vol 2 (2) ◽  
pp. 112-117 ◽  
Author(s):  
Ruzhica Bogeska ◽  
Heike L. Pahl
Keyword(s):  
Stem Cell ◽  
Polycythemia Vera ◽  
Hematopoietic Stem Cell ◽  
Nuclear Factor ◽  
Hematopoietic Stem ◽  
Myeloid Progenitor ◽  
Erythroid Maturation

The Ski oncoprotein regulates Hematopoietic Stem Cell Fitness and Functions as a Corepressor for Gfi1.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1403-1403
Author(s):  
Chinavenmeni S. Velu ◽  
Michael Berk ◽  
Haiming Xu ◽  
Tristan Bourdeau ◽  
Avedis Kazanjian ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Target Genes ◽  
Fetal Liver ◽  
Embryonic Stem ◽  
Loss Of Function ◽  
Hematopoietic Stem ◽  
Myeloid Progenitor ◽  
Multipotent Progenitors

Abstract Ski is a corepressor protein originally identified as a retrovirally transduced oncoprotein. Genetic deletion of Ski has revealed essential roles in multiple developmental processes. Suggestion that Ski may play a role in hematopoiesis first came from expression of v-Ski and c-Kit, which induced the continuous in vitro growth of primary avian multipotent progenitors. However, the hematopoietic phenotype of Ski−/− mice has not been described. Here, we show that Ski loss of function results in loss of hematopoietic stem cell (HSC) fitness and abnormal regulation of myeloid progenitor numbers. Fetal liver Ski−/− HSC engraft well in ablated recipients, but are not competitive in engraftment. Moreover, Ski null embryonic stem cells generate many tissues in chimeras, but infrequently participate in hematopoiesis. Thus, Ski null HSC are not competitive in both transplant and chimera settings, indicating a defect in stem cell fitness. Engrafted Ski−/− fetal liver cells generate fewer myeloid lineage cells than wild type littermates, and accumulate granulocytemonocyte progenitors. Growth factor independent -1 (Gfi1) is a transcriptional repressor that controls HSC maintenance and myeloid progenitor differentiation. Gfi1−/− and Ski−/− hematopoietic stem and myeloid progenitor phenotypes are strikingly similar. We find that Ski functions as a corepressor for Gfi1. Both endogenous and synthetic Gfi1 and Ski physically interact in vitro and upon Gfi1 target genes. Knockdown of Gfi1 or Ski results in derepression of these targets. Thus, our results provide a molecular link between the similar HSC and myeloid progenitor phenotypes engendered by Gfi1 or Ski deletion.

scholarly journals FLVCR is necessary for erythroid maturation, may contribute to platelet maturation, but is dispensable for normal hematopoietic stem cell function

Blood ◽  
2013 ◽  
Vol 122 (16) ◽  
pp. 2903-2910 ◽  
Author(s):  
John C. H. Byon ◽  
Jing Chen ◽  
Raymond T. Doty ◽  
Janis L. Abkowitz
Keyword(s):  
Stem Cell ◽  
Steady State ◽  
Hematopoietic Stem Cell ◽  
Cell Function ◽  
Stress Conditions ◽  
Hematopoietic Stem ◽  
Platelet Counts ◽  
Key Points ◽  
Erythroid Maturation

Key Points FLVCR deletion causes proerythroblast apoptosis and lethal anemia but leads to increased megakaryocyte ploidy and platelet counts. Loss of FLVCR is dispensable for hematopoietic stem cell function during steady-state and stress conditions.

HMGA2, a Member of the High Mobility Group Gene Family, Is Expressed at the Protein Level in Peripheral Blood CD34+ Cells of Patients with Idiopathic Myelofibrosis and Polycythemia Vera.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 798-798 ◽  
Author(s):  
Stephen Huang ◽  
Minjiang Xu ◽  
Edward Bruno ◽  
Giovanni Barosi ◽  
Josef Prchal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Polycythemia Vera ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
High Mobility ◽  
Idiopathic Myelofibrosis ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Hmga2 Protein ◽  
Cell Defect

Idiopathic myelofibrosis (IM) is a chronic myeloproliferative disorder associated with increased numbers of CD34+ cells circulating in the peripheral blood (PB). To characterize these cells, we transplanted CD34+ or CD34− cells from either G-CSF mobilized PB or IM PB into NOD/SCID mice to test their hematopoietic stem cell function. IM CD34+ cells, but not CD34−, cells engrafted in NOD/SCID mice, demonstrating that IM PB CD34+ cells contain true bone marrow repopulating cells. Furthermore, the differentiation program of IM CD34+ cells was quite different than that of CD34+ cells isolated from normal donors receiving G-CSF. G-CSF mobilized PB CD34+ cells generated predominantly CD19+ cells (B-lymphocytes), while IM PB CD34+ cells generated predominantly myeloid cells as well as larger numbers of CD41+ cells (megakaryocytes), but few CD19+ cells. The molecular basis for this stem cell defect in IM remains poorly defined. We hypothesized that the High Mobility Group Gene, HMGA2, might play a role in the biogenesis of IM. HMGA2 is a nuclear protein, normally expressed only during embryonic and fetal development, which acts as an architectural transcription factor important in the growth and differentiation of cells of mesenchymal origin. It has been reported that this gene has a direct effect on chromatin configuration by promoting DNA relaxation and that it may control the transcriptional activities of several genes. Rearrangement of the HMGA2 gene has frequently been detected in human benign tumors of mesenchymal origin including lipomas and sarcomas. In addition, the gene has been shown to be overexpressed in squamous cell carcinomas of the oral cavity. Previous work has suggested that HMGA2 is overexpressed in the PB mononuclear cells of patients with IM at the mRNA level (Andrieux, J. et al, Genes, Chromosomes & Cancer, 39: 82, 2004). Since IM and polycythemia vera (PV) are hematological malignancies that originate at the level of the hematopoietic stem cell, we examined the expression of HMGA2 in CD34+ and CD34− cell fractions isolated from the PB of patients with IM and PV as well as G-CSF mobilized normal donors. Using Western Blotting, we were unable to detect HMGA2 protein in either G-CSF mobilized CD34+ or CD34− cells. By contrast, HMGA2 was clearly expressed in the CD34+ cell fraction, but not the CD34− fraction isolated from IM and PV patients. These data indicate that increased HMGA2 protein levels are unique to IM and PV CD34+ cells and that the aberrant expression of this gene in the CD34+ progenitor cells may contribute to the stem cell defect in these myeloproliferative disorders.

scholarly journals B-myb is an essential regulator of hematopoietic stem cell and myeloid progenitor cell development

2014 ◽  
Vol 111 (8) ◽  
pp. 3122-3127 ◽  
Author(s):  
S. J. Baker ◽  
A. Ma'ayan ◽  
Y. K. Lieu ◽  
P. John ◽  
M. V. R. Reddy ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Progenitor Cell ◽  
Cell Development ◽  
Hematopoietic Stem ◽  
Myeloid Progenitor ◽  
Myeloid Progenitor Cell
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