Analysis of the Gata1-dependent Spi1 cistrome in mouse BFU-Es erythroid progenitor and MEL bone marrow erythroid progenitor cells

2019 ◽  
Author(s):  
SN Wontakal
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

scholarly journals Ligand-dependent repression of the erythroid transcription factor GATA-1 by the estrogen receptor.

1995 ◽  
Vol 15 (6) ◽  
pp. 3147-3153 ◽  
Author(s):  
G A Blobel ◽  
C A Sieff ◽  
S H Orkin
Keyword(s):  
Bone Marrow ◽  
Estrogen Receptor ◽  
Transcription Factor ◽  
Progenitor Cells ◽  
Erythroid Cell ◽  
High Dose ◽  
Dependent Manner ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

High-dose estrogen administration induces anemia in mammals. In chickens, estrogens stimulate outgrowth of bone marrow-derived erythroid progenitor cells and delay their maturation. This delay is associated with down-regulation of many erythroid cell-specific genes, including alpha- and beta-globin, band 3, band 4.1, and the erythroid cell-specific histone H5. We show here that estrogens also reduce the number of erythroid progenitor cells in primary human bone marrow cultures. To address potential mechanisms by which estrogens suppress erythropoiesis, we have examined their effects on GATA-1, an erythroid transcription factor that participates in the regulation of the majority of erythroid cell-specific genes and is necessary for full maturation of erythrocytes. We demonstrate that the transcriptional activity of GATA-1 is strongly repressed by the estrogen receptor (ER) in a ligand-dependent manner and that this repression is reversible in the presence of 4-hydroxytamoxifen. ER-mediated repression of GATA-1 activity occurs on an artificial promoter containing a single GATA-binding site, as well as in the context of an intact promoter which is normally regulated by GATA-1. GATA-1 and ER bind to each other in vitro in the absence of DNA. In coimmunoprecipitation experiments using transfected COS cells, GATA-1 and ER associate in a ligand-dependent manner. Mapping experiments indicate that GATA-1 and the ER form at least two contacts, which involve the finger region and the N-terminal activation domain of GATA-1. We speculate that estrogens exert effects on erythropoiesis by modulating GATA-1 activity through protein-protein interaction with the ER. Interference with GATA-binding proteins may be one mechanism by which steroid hormones modulate cellular differentiation.

Anti-HIV drugs: Comparative toxicities in murine fetal liver and bone marrow erythroid progenitor cells

Life Sciences ◽  
1989 ◽  
Vol 45 (4) ◽  
pp. iii-vii ◽  
Author(s):  
Sudhir R. Gogu ◽  
Barbara S. Beckman ◽  
Krishna C. Agrawal
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Fetal Liver ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Hiv Drugs ◽  
Anti Hiv

scholarly journals Inhibition of Immature Erythroid Progenitor Cell Proliferation by Macrophage Inflammatory Protein-1α by Interacting Mainly With a C-C Chemokine Receptor, CCR1

Blood ◽  
1997 ◽  
Vol 90 (2) ◽  
pp. 605-611 ◽  
Author(s):  
Shao-bo Su ◽  
Naofumi Mukaida ◽  
Jian-bin Wang ◽  
Yi Zhang ◽  
Akiyoshi Takami ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells ◽  
Inflammatory Protein ◽  
Cd34 Cells ◽  
Macrophage Inflammatory Protein ◽  
Marrow Cells

Abstract Several lines of evidence indicate that macrophage inflammatory protein-1α (MIP-1α) modulates the proliferation of hematopoietic progenitor cells, depending on their maturational stages. To clarify the mechanisms for the modulation of hematopoiesis by this chemokine, we examined the expression of a receptor for MIP-1α, CCR1, on bone marrow cells of normal individuals using a specific antibody and explored the effects of MIP-1α on in vitro erythropoiesis driven by stem cell factor (SCF) and erythropoietin (Epo). CCR1 was expressed on glycophorin A-positive erythroblasts in addition to lymphocytes and granulocytes. CCR1+ cells, isolated from bone marrow mononuclear cells (BMMNCs) using a cell sorter, comprised virtually all erythroid progenitor cells in the BMMNCs. Moreover, MIP-1α inhibited, in a dose-dependent manner, colony formation by burst-forming unit-erythroid (BFU-E), but not by colony forming unit-erythroid (CFU-E), in a methylcellulose culture of purified human CD34+ bone marrow cells. Although reverse-transcription polymerase chain reaction (RT-PCR) showed the presence of CCR1, CCR4, and CCR5 transcripts in CD34+ cells in BM, anti-CCR1 antibodies significantly abrogated the inhibitory effects of MIP-1α on BFU-E formation both in a methylcellulose culture and in a single cell proliferation assay of purified CD34+ cells. Although the contribution of CCR4 or CCR5 cannot be completely excluded, these results suggest that MIP-1α–mediated suppression of the proliferation of immature, but not mature erythroid progenitor cells, is largely mediated by CCR1 expressed on these progenitor cells.

Lineage-Specific Activation of p53 in Response to Ribosomal Haploinsufficiency in Human Bone Marrow Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 948-948
Author(s):  
Shilpee Dutt ◽  
Anupama Narla ◽  
Jeffery Lorne Kutok ◽  
Benjamin L. Ebert
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Ribosome Biogenesis ◽  
Conflicts Of Interest ◽  
Erythroid Cell ◽  
Erythroid Progenitor ◽  
Intense Staining ◽  
Bone Marrow Biopsies ◽  
Erythroid Progenitor Cells ◽  
Cd34 Cells

Abstract Abstract 948 Haploinsufficiency for the ribosomal protein genes RPS14 and RPS19 have been implicated in the erythroid defect in the 5q- syndrome and Diamond Blackfan Anemia, respectively. However, the mechanism by which defective ribosome biogenesis causes erythroid failure is unknown. In this study, we found that shRNA mediated knockdown of RPS14 or RPS19 in primary human CD34+ cells stabilize TP53 by day 4 after infection with concomitant arrest of these cells at G1 stage of cell cycle. The levels of TP53 attained are comparable to the levels observed following gamma irradiation (5Gy) of the CD34+ cells. Using quantitative PCR, we confirmed that stabilized TP53 activates expression of downstream target genes MDM2, p21, Bax and Wig-1. Furthermore, treatment of the CD34+ cells with Nutlin-3 phenocopies RPS14 or RPS19 knockdown, suggesting that the mechanism of TP53 activation is mediated by MDM2 pathway. Conversely, treatment with pifithrin-alpha, which inhibits the transactivation activity of TP53, rescues the effects of RPS14 or RPS19 knockdown. The in vitro activation of TP53 in CD34+ cells was restricted to erythroid cell lineage, consistent with the clinical phenotype of RPS14 or RPS19 haploinsufficiency. Moreover, immunohistochemical analysis of bone marrow biopsies from patient with the 5q- syndrome demonstrated intense staining of TP53 that was restricted to erythroid progenitor cells. Taken together our study indicates that inhibition of ribosomal biogenesis causes TP53 activation selectively in erythroid progenitor cells. Clinically, TP53 staining of patient samples could be used as a diagnostic marker for some types of MDS. Disclosures: No relevant conflicts of interest to declare.

Receptor binding cancer antigen expressed on SiSo cells, a novel regulator of apoptosis of erythroid progenitor cells

Blood ◽  
2001 ◽  
Vol 98 (2) ◽  
pp. 313-321 ◽  
Author(s):  
Takamitsu Matsushima ◽  
Manabu Nakashima ◽  
Koichi Oshima ◽  
Yasunobu Abe ◽  
Junji Nishimura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Receptor Binding ◽  
Transferrin Receptor ◽  
Human Peripheral Blood ◽  
Soluble Form ◽  
Glycophorin A ◽  
Cancer Antigen ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cells

To better understand the control of apoptosis during erythropoiesis, this study investigated the role of a novel tumor-associated antigen, RCAS1 (receptor binding cancer antigen expressed on SiSo cells), with regard to the regulation of apoptosis of erythroid progenitor cells. Erythroid colony-forming cells (ECFCs) purified from human peripheral blood were used. Binding experiments of RCAS1 showed that ECFCs abundantly expressed receptors (RCAS1R) for RCAS1 and that the degree of binding of RCAS1 to the receptors diminished rapidly during erythroid maturation in vitro. When the soluble form of RCAS1 was added to the cultures, ECFCs underwent apoptosis, including collapse of the mitochondrial transmembrane potential, and activation of caspases 8 and 3. The addition of an anti-Fas blocking antibody or Fas-Fc failed to reduce the apoptosis induced by RCAS1, thereby indicating that effects of RCAS1 are independent of Fas activation. When binding of RCAS1 to normal bone marrow cells was analyzed, RCAS1R was evident on cells with an immature erythroid phenotype (transferrin receptor+/glycophorin A−) but not with a mature phenotype (transferrin receptor−/glycophorin A+). Histochemical staining revealed the expression of RCAS1 in the cytoplasm of bone marrow macrophages. These findings indicate that RCAS1, which is mainly produced by macrophages in hematopoietic tissue, may have a crucial role in controlling erythropoiesis by modulating apoptosis of erythroid progenitor cells via a Fas-independent mechanism.

MTG16, a Target of the T(16;21) in Acute Myeloid Leukemia, Is Required for Hematopoietic Stem and Progenitor Cell Functions

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 609-609
Author(s):  
Melissa Ann Steapleton ◽  
Isabel Moreno ◽  
Brenda Chyla ◽  
Scott Hiebert
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Rapid Expansion ◽  
Erythroid Progenitor ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Cell Functions ◽  
Erythroid Progenitor Cells

Abstract The t(8;21) and t(16;21) disrupt two closely related Myeloid Translocation Gene family members respectively, MTG8 and MTG16. Whereas the expression of MTG8 is highly regulated, MTG16 is more widely expressed and is the family member most highly expressed in hematopoietic stem cells. Therefore, to address the contribution of MTG16 to HSC functions and hematopoiesis, we created mice lacking this gene. We show that this transcriptional co-repressor is required for hematopoietic stem and progenitor cell functions such as cell fate decisions and early progenitor cell proliferation. Inactivation of Mtg16 skewed early myeloid progenitor cells towards the granulocytic/macrophage lineage, while reducing the numbers of megakaryocyte-erythroid progenitor cells, which was shown using both flow cytometry and methylcellulose colony formation assays. In addition, inactivation of Mtg16 impaired the rapid expansion of long and short-term stem cells, multi-potent progenitor cells and megakaryocyte-erythroid progenitor cells that are required under hematopoietic stress/emergency. Due to this, the Mtg16-null mice could not respond to phenylhydrazine or 5-fluorouracil treatment and were completely defective in the colony forming unit-spleen (CFU-S) assays. Additionally, Mtg16-null bone marrow failed to repopulate the hematopoietic system when it was transplanted into an irradiated recipient mouse and also failed to compete with wild-type bone marrow in a competitive bone marrow transplant. This impairment appeared to be due to a failure to proliferate rather than an induction of cell death, as expression of c-Myc, but not Bcl2, complemented the Mtg16(−/−) defect. Thus, like other key transcriptional co-repressors (e.g., the retinoblastoma protein, pRB, and the nuclear hormone co-repressor, N-CoR) Mtg16 is a key regulator of stem cell functions and lineage commitment in hematopoiesis.

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