scholarly journals The Role of ErbB2 Signaling in the Onset of Terminal Differentiation of OligodendrocytesIn Vivo

2003 ◽  
Vol 23 (13) ◽  
pp. 5561-5571 ◽  
Author(s):  
Ju Young Kim ◽  
Qin Sun ◽  
Michael Oglesbee ◽  
Sung Ok Yoon
Keyword(s):  
Terminal Differentiation ◽  
Erbb2 Signaling

scholarly journals Interleukin-6 and the Granulocyte Colony-Stimulating Factor Receptor Are Major Independent Regulators of Granulopoiesis In Vivo But Are Not Required for Lineage Commitment or Terminal Differentiation

Blood ◽  
1997 ◽  
Vol 90 (7) ◽  
pp. 2583-2590 ◽  
Author(s):  
Fulu Liu ◽  
Jennifer Poursine-Laurent ◽  
Huai Yang Wu ◽  
Daniel C. Link
Keyword(s):  
Interleukin 6 ◽  
Terminal Differentiation ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Normal Numbers ◽  
Stimulating Factor ◽  
Deficient Mice ◽  
Additional Loss

Multiple hematopoietic cytokines can stimulate granulopoiesis; however, their relative importance in vivo and mechanisms of action remain unclear. We recently reported that granulocyte colony-stimulating factor receptor (G-CSFR)-deficient mice have a severe quantitative defect in granulopoiesis despite which phenotypically normal neutrophils were still detected. These results confirmed a role for the G-CSFR as a major regulator of granulopoiesis in vivo, but also indicated that G-CSFR independent mechanisms of granulopoiesis must exist. To explore the role of interleukin-6 (IL-6) in granulopoiesis, we generated IL-6 × G-CSFR doubly deficient mice. The additional loss of IL-6 significantly worsened the neutropenia present in young adult G-CSFR–deficient mice; moreover, exogenous IL-6 stimulated granulopoiesis in vivo in the absence of G-CSFR signals. Near normal numbers of myeloid progenitors were detected in the bone marrow of IL-6 × G-CSFR–deficient mice and their ability to terminally differentiate into mature neutrophils was observed. These results indicate that IL-6 is an independent regulator of granulopoiesis in vivo and show that neither G-CSFR or IL-6 signals are required for the commitment of multipotential progenitors to the myeloid lineage or for their terminal differentiation.

scholarly journals The Critical Role of 15-Lipoxygenase-1 in Colorectal Epithelial Cell Terminal Differentiation and Tumorigenesis

2005 ◽  
Vol 65 (24) ◽  
pp. 11486-11492 ◽  
Author(s):  
Imad Shureiqi ◽  
Yuanqing Wu ◽  
Dongning Chen ◽  
Xiu L. Yang ◽  
Baoxiang Guan ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Critical Role ◽  
Terminal Differentiation

scholarly journals Role of 1,25-dihydroxycholecalciferol in growth-plate cartilage: inhibition of terminal differentiation of chondrocytes in vitro and in vivo.

1990 ◽  
Vol 87 (17) ◽  
pp. 6522-6526 ◽  
Author(s):  
Y. Kato ◽  
A. Shimazu ◽  
M. Iwamoto ◽  
K. Nakashima ◽  
T. Koike ◽  
...  
Keyword(s):  
Growth Plate ◽  
Terminal Differentiation ◽  
Growth Plate Cartilage

scholarly journals Prostacyclin as a potent effector of adipose-cell differentiation

1989 ◽  
Vol 257 (2) ◽  
pp. 399-405 ◽  
Author(s):  
R Négrel ◽  
D Gaillard ◽  
G Ailhaud
Keyword(s):  
Arachidonic Acid ◽  
Cyclic Amp ◽  
Critical Role ◽  
Terminal Differentiation ◽  
Prostaglandin F2 Alpha ◽  
Adipogenic Effect ◽  
Adipose Cells

The terminal differentiation of Ob1771 pre-adipose cells induced by arachidonic acid in serum-free hormone-supplemented medium containing insulin, transferrin, growth hormone, tri-iodothyronine and fetuin (5F medium) was strongly diminished in the presence of inhibitors of prostaglandin synthesis, namely aspirin or indomethacin. Carbaprostacyclin, a stable analogue of prostacyclin (prostaglandin I2) known to be synthesized by pre-adipocytes and adipocytes, behaved as an efficient activator of cyclic AMP production and was able, when added to 5F medium, to mimic the adipogenic effect of arachidonic acid. Prostaglandins E2, F2 alpha and D2, unable to affect the cyclic AMP production, failed to substitute for carbaprostacyclin. However, prostaglandin F2 alpha, which is another metabolite of arachidonic acid in pre-adipose and adipose cells, able to promote inositol phospholipid breakdown and protein kinase C activation, potentiated the adipogenic effect of carbaprostacyclin. In addition, carbaprostacyclin enhanced both a limited proliferation and terminal differentiation of adipose precursor cells isolated from rodent and human adipose tissues maintained in primary culture. These results demonstrate the critical role of prostacyclin and prostaglandin F2 alpha on adipose conversion in vitro and suggest a paracrine/autocrine role of both prostanoids in the development of adipose tissue in vivo.

scholarly journals Bcl2 inhibits apoptosis associated with terminal differentiation of HL- 60 myeloid leukemia cells

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2261-2267 ◽  
Author(s):  
L Naumovski ◽  
ML Cleary
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Myeloid Cells ◽  
Terminal Differentiation ◽  
Retroviral Gene Transfer ◽  
Protein Levels ◽  
All Trans Retinoic Acid ◽  
Bcl2 Protein ◽  
The Relationship

Abstract The Bcl2 protein inhibits apoptosis (programmed cell death) induced by a variety of noxious stimuli. However, relatively little is known about its effect on apoptosis that occurs after terminal differentiation. Bcl2 protein levels decrease during differentiation of myeloid cells into granulocytes that subsequently undergo apoptosis, but the potential role of Bcl2 in coupling survival and differentiation remains undefined. To ascertain the relationship between decreasing Bcl2 levels and the onset of apoptosis in differentiating myeloid cells, Bcl2 was hyperexpressed in the HL-60 cell line after retroviral gene transfer. After treatment of HL-60/BCL2 cells with all-trans retinoic acid or phorbol myristic acid, Bcl2 levels did not decrease as in normal HL-60 cells but, rather, increased because of activation of the viral promoter. Differentiation of the Bcl2-overexpressing cells was similar to that of normal HL-60 cells, but they showed little evidence for apoptosis and had a prolonged survival. These studies show that the survival-enhancing properties of Bcl2 counteract programmed cell death that accompanies terminal differentiation; however, Bcl2 has no significant effect on differentiation itself, suggesting that apoptosis and differentiation are regulated independently in myeloid cells.

Role of miR-30a-5p and miR-26a-5p in induction of terminal differentiation in human K562 erythroleukemia cells

Cytotherapy ◽  
2020 ◽  
Vol 22 (5) ◽  
pp. S191
Author(s):  
R. Kronstein-Wiedemann ◽  
J. Thiel ◽  
P. Milanov ◽  
E. Pasini ◽  
T. Tonn
Keyword(s):  
Terminal Differentiation ◽  
Erythroleukemia Cells

Essential Role of Pro-Apoptotic Mechanisms for Production of Normal Erythrocytes and Prevention of Hemolysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 426-426 ◽  
Author(s):  
Min Chen ◽  
Josef T. Prchal ◽  
Sandoval Hector ◽  
Perumal Thiagarajan ◽  
Swapan K. Dasgupta ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Family Member ◽  
Peripheral Blood ◽  
Mitochondrial Membrane ◽  
Essential Role ◽  
Molecular Mechanisms ◽  
Terminal Differentiation ◽  
Erythroid Precursors ◽  
Erythroid Maturation

Abstract Prevention of apoptosis is a well-recognized mechanism essential for productive early erythropoiesis and preventing anemia; however, the importance of pro-apoptotic processes for productive terminal erythropoiesis is not defined. Erythroid cells undergo enucleation and the removal of organelles during terminal differentiation. Although autophagy has been shown to mediate the elimination of organelles for erythroid maturation, the molecular mechanisms underlying this process remain unknown. Here we report a novel role for Bnip3L, a pro-apoptotic Bcl-2 family member, in the regulation of erythroid maturation through autophagy. Bnip3L−/− mice developed hemolytic anemia and expansion of erythroid precursors (Fig.1A). Moreover, erythrocytes in the peripheral blood of Bnip3L−/− mice exhibited mitochondrial retention associated with reduced lifespan (Fig. 1B). While the clearance of ribosomes proceeded normally in the absence of Bnip3L, the entry of mitochondria into autophagosomes was defective (Fig. 1C). Overexpression of Bnip3L led to the loss of mitochondrial membrane potential (ΔΨm). Further, disrupting Δ Ψ m with an uncoupling chemical restored the sequestration of mitochondria into autophagosomes in Bnip3L−/− erythrocytes (Fig. 1C). Our study indicates that Bnip3L-dependent loss of Δ Ψ m is important for targeting the mitochondria into autophagosomes for degradation during erythroid maturation, and interference with this function impairs terminal erythroid maturation and results in hemolysis. These data underlie the importance of pro-apoptotic mechanisms for productive terminal erythropoiesis through autophagy. Figure Figure

Tropomodulin3-Null Mice Are Embryonic Lethal with Anemia Due to Defects in Erythroblast Enucleation and Erythroblast-Macrophage Islands in the Fetal Liver

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 84-84
Author(s):  
Velia M. Fowler ◽  
Zhenhua Sui ◽  
Roberta B. Nowak ◽  
Nancy E. Kim ◽  
Andrea Bacconi
Keyword(s):  
Late Stage ◽  
Fetal Liver ◽  
Terminal Differentiation ◽  
Wild Type ◽  
Contractile Ring ◽  
Mild Phenotype ◽  
Ring Assembly ◽  
Embryonic Lethal ◽  
Definitive Erythropoiesis

Abstract Abstract 84 Tropomodulin1 (Tmod1) binds tropomyosin and caps the pointed ends of the short actin filaments in the spectrin-actin network of red blood cells (RBCs). Tmod1-null mice display a mild sphero-elliptocytic anemia due to mis-regulation of actin filament lengths and a disrupted membrane skeleton. The mild phenotype may be explained by the compensation of Tmod3, which is not found in wild-type RBCs but exists in Tmod1-null RBCs (one-fifth level of Tmod1). Our experiments with human erythroblasts show that the expression of Tmod1 increases during terminal differentiation while the level of Tmod3 is relatively constant, only decreasing at a very late stage. To investigate the role of Tmod3 in RBCs, we created a Tmod3 knockout mouse from ES cells (#RRF004, BayGenomics) with a gene-trap vector insertion into intron 1 of Tmod3. Both RT-PCR and western-blot results show that the expression of Tmod3 is abolished in Tmod3−/− mice. Tmod3+/− mice are viable and fertile, while Tmod3−/− animals are embryonic lethal, with most nulls dying between E16.5-E17.5. Tmod3−/− embryos are pale and anemic with a smaller fetal liver, suggesting that the lethality might be due to defective definitive erythropoiesis. This is supported by analysis of peripheral blood, which shows fewer definitive enucleated erythroblasts in Tmod3-null embryos. Flow-cytometry of fetal liver erythroblasts labeled with Ter119 and CD71 indicates that the late stage R3 population is reduced by about one-third in absence of Tmod3, while R1-R2 populations are somewhat increased. In addition, Annexin V staining shows a two-fold increase in apoptotic cells in the fetal liver, most of which are in the R1 population. Measurement of enucleation frequency in R populations shows a marked reduction of enucleated cells as the erythroblasts mature through the R3-R5 populations. These data indicate that definitive erythropoiesis is defective due to impaired erythroblast terminal differentiation in absence of Tmod3. To determine the underlying mechanisms, we used histology and confocal fluorescence microscopy to investigate the morphology and actin cytoskeleton of erythroblasts in process of enucleation. These experiments show abnormal nuclear morphology in orthochromatic Tmod3-null fetal liver erythroblasts, as well as defective F-actin contractile ring assembly in Tmod3−/− erythroblasts in process of nuclear expulsion, suggesting a role for Tmod3 in enucleation. Since macrophages are required for production of definitive erythroblasts and enucleation in vivo, we explored the role of macrophages in the Tmod3−/− phenotype. Immunofluorescence staining of fetal liver cryosections with F4/80, Ter119 and Hoechst reveals that macrophages display strikingly less dendritic morphologies in the Tmod3−/− mice, with macrophages sometimes containing Ter119-positive nucleated erythroblasts. Isolation of native erythroblast-macrophage islands from fetal liver demonstrates that islands isolated from Tmod3−/− fetal livers contain fewer erythroblasts compared with those from wild-type fetal liver. Further, reconstitution experiments indicate that erythroblasts from Tmod3−/− fetal liver are unable to form normal islands, indicating that Tmod3 function is required in erythroblasts. In conclusion, our study shows that knockout of Tmod3 leads to defective definitive erythropoiesis and embryonic lethality in mice, due to defects in island formation and abnormal enucleation. These data suggest that Tmod3-mediated actin remodeling may be required for erythroblast-macrophage adhesion as well as contractile ring assembly during erythroblast enucleation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Role of Neuregulin-1/ErbB2 Signaling in Endothelium-Cardiomyocyte Cross-talk

2006 ◽  
Vol 281 (28) ◽  
pp. 19469-19477 ◽  
Author(s):  
Katrien Lemmens ◽  
Vincent F. M. Segers ◽  
Marc Demolder ◽  
Gilles W. De Keulenaer
Keyword(s):  
Cross Talk ◽  
Neuregulin 1 ◽  
Erbb2 Signaling

scholarly journals Proto-oncogenes of the fos/jun family of transcription factors are positive regulators of myeloid differentiation.

1993 ◽  
Vol 13 (2) ◽  
pp. 841-851 ◽  
Author(s):  
K A Lord ◽  
A Abdollahi ◽  
B Hoffman-Liebermann ◽  
D A Liebermann
Keyword(s):  
Transcription Factors ◽  
Leucine Zipper ◽  
Culture Media ◽  
Terminal Differentiation ◽  
Cell Types ◽  
Primary Response ◽  
Myeloid Differentiation ◽  
Active Transcription

The proto-oncogenes c-jun, junB, junD, and c-fos recently have been shown to encode for transcription factors with a leucine zipper that mediates dimerization to constitute active transcription factors; juns were shown to dimerize with each other and with c-fos, whereas fos was shown to dimerize only with juns. After birth, hematopoietic cells of the myeloid lineage, and some other terminally differentiated cell types, express high levels of c-fos. Still, the role of fos/jun transcription factors in normal myelopoiesis or in leukemogenesis has not been established. Recently, c-jun, junB, and junD were identified as myeloid differentiation primary response genes stably expressed following induction of terminal differentiation of myeloblastic leukemia M1 cells. Intriguingly, c-fos, though induced during normal myelopoiesis, was not induced upon M1 differentiation. To gain further insights into the role of fos/jun in normal myelopoiesis and leukemogenicity, M1fos and M1junB cell lines, which constitutively express c-fos and junB, respectively, were established. It was shown that enforced expression of c-fos, and to a lesser extent junB, in M1 cells results in both an increased propensity to differentiate and a reduction in the aggressiveness of the M1 leukemic phenotype. M1fos cells constitutively expressed immediate-early and late genetic markers of differentiated M1 cells. The in vitro differentiation of normal myeloblasts into mature macrophages and granulocytes, as well as the increased propensity of M1fos leukemic myeloblasts to be induced for terminal differentiation, was dramatically impaired with use of c-fos antisense oligomers in the culture media. Taken together, these observations show that the proto-oncogenes which encode for fos/jun transcription factors play important roles in promoting myeloid differentiation. The ability of the M1 leukemic myeloblasts to be induced for terminal differentiation in the absence of apparent fos expression indicates that there is some redundancy among the fos/jun family of transcription factors in promoting myeloid differentiation; however, juns alone cannot completely compensate for the lack of fos. Thus, genetic lesions affecting fos/jun expression may play a role in the development of "preleukemic" myelodysplastic syndromes and their further progression to leukemias.

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