Stem cell factor and leukemia inhibitory factor promote primordial germ cell survival by suppressing programmed cell death (apoptosis)

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1089-1094 ◽  
Author(s):  
M. Pesce ◽  
M.G. Farrace ◽  
M. Piacentini ◽  
S. Dolci ◽  
M. De Felici
Keyword(s):  
Cell Death ◽  
Stem Cell ◽  
Programmed Cell Death ◽  
Leukemia Inhibitory Factor ◽  
Stem Cell Factor ◽  
Tissue Transglutaminase ◽  
Primordial Germ Cell ◽  
Inhibitory Factor ◽  
High Level

Proliferating primordial germ cells (PGCs) isolated from mouse embryos soon after their arrival in the genital ridges would only survive in vitro at temperature of less than 30 degrees C (De Felici, M. and McLaren, A. (1983). Exp. Cell. Res. 144, 417–427; Wabik-Sliz, B. and McLaren, A. (1984). Exp. Cell. Res. 154, 530–536) or when co-cultured on cell feeder layers (Donovan, P. J., Stott, D., Godin, I., Heasman, J. and Wylie, C. C. (1986). Cell 44, 831–838; De Felici, M. and Dolci, S. (1991). Dev. Biol. 147, 281–284). In the present paper we report that mouse PGC death in vitro occurs with all the hallmarks of programmed cell death or apoptosis. We found that after 4–5 hours in culture many PGCs isolated from 12.5 dpc fetal gonads assumed a nuclear morphology and produced membrane bound fragments (apoptotic bodies) typical of apoptotic cells. In addition, PGCs in culture accumulated high level of tissue transglutaminase (tTGase; an enzyme that is induced and activated during apoptosis) and showed extensive degradation of DNA to oligonucleosomal fragments, which is characteristic of apoptosis. The physiological relevance of this mechanism of PGC death is supported by the finding that some PGCs undergoing apoptosis, as revealed by the high level of tTGase expression, were detected in the embryo. Most importantly, we show that the addition of stem cell factor (SCF) or leukemia inhibitory factor (LIF) to the culture medium, two cytokines known to favour PGC survival and/or proliferation in vitro, markedly reduced the occurrence of apoptosis in PGCs during the first hours in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of the recombinant hematopoietic growth factors interleukin-3, interleukin-6, stem cell factor, and leukemia inhibitory factor on the megakaryocytic differentiation of CD34+ cells

Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 84-95 ◽  
Author(s):  
N Debili ◽  
JM Masse ◽  
A Katz ◽  
J Guichard ◽  
J Breton-Gorius ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Leukemia Inhibitory Factor ◽  
Stem Cell Factor ◽  
Liquid Culture ◽  
Cell Concentration ◽  
Inhibitory Factor ◽  
Concentration Addition ◽  
Potent Inducer ◽  
Cd34 Cells

Using a liquid culture system and human CD34+ marrow cells, we examined the effects of recombinant interleukin (IL)-3, IL-6, stem cell factor (SCF), and leukemia inhibitory factor (LIF) on megakaryocyte (MK) growth, endoreplication, and maturation. MK proliferation, ploidy distribution, and volume were studied by flow cytometry. IL-3 was the only cytokine that, alone, induced a marked increase in MK proliferation. At a high CD34+ cell concentration, addition of IL-6, SCF, and LIF to IL-3--containing medium increased the number of MK (approximately 20%). At a low CD34+ cell concentration, IL-3 alone was a less potent inducer of MK growth, but IL-6, SCF, and their combination had a marked effect, increasing the number of MK by a factor 1.7, 2.9, and 4.4, respectively. These differences may be related to the endogenous release of cytokines in the culture. The effects of these cytokines were subsequently tested on a more mature type of MK progenitor (CD34+ cells isolated after 6 days of incubation in liquid culture). IL-3 remained the most potent cytokine, but IL-6 or SCF alone also increased MK number in comparison to unstimulated cultures. The ploidy distribution of MKs grown with IL-3 was not markedly changed by the addition of the other cytokines, with the exception of SCF, which induced a significant increase in the mean ploidy. However, in all cultures, glycoprotein (GP)IIIa+ 2N and 4N cells were present in large but variable numbers (35% to 75%). The number of these low-ploidy MKs directly correlated with MK proliferation. Therefore, we subsequently explored the absolute number of polyploid MK produced in culture. SCF, IL-6, or their combination, in association with IL-3, increased the number of polyploid MK up to fourfold. In addition, they improved the maturation of MK grown in the presence of IL-3, leading to the synthesis of demarcation membranes and platelet shedding. A similar effect of growth factors on the maturation of day 6 CD34+ cells was observed. We conclude that IL-6 and SCF have a broad range of activities on megakaryocytopoiesis, acting both on the early and late stages. However, the proliferative properties of these cytokines largely predominate in our cultures. Therefore, in the absence of a specific MK regulator, this study further extends the need for a combination of growth factors to maximize megakaryocytopoiesis.

scholarly journals Effects of 6-bromoindirubin-3′-oxime on the maintenance of pluripotency of porcine embryonic germ cells in combination with stem cell factor, leukemia inhibitory factor and fibroblast growth factor

Reproduction ◽  
2010 ◽  
Vol 139 (6) ◽  
pp. 1039-1046 ◽  
Author(s):  
Jiang Wen ◽  
Juan Liu ◽  
Guangqi Song ◽  
Limei Liu ◽  
Bo Tang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Germ Cells ◽  
Leukemia Inhibitory Factor ◽  
Stem Cell Factor ◽  
Glycogen Synthase ◽  
Embryoid Bodies ◽  
Inhibitory Factor ◽  
Fibroblast Growth

6-Bromoindirubin-3′-oxime (BIO), which is one of the glycogen synthase kinase 3 inhibitors and a key regulator of numerous signaling pathways, was reported to be capable of maintaining the pluripotency of human and mouse embryonic stem cells. Presently, it is unknown whether BIO can influence the derivation of porcine embryonic germ (EG) cells. In this study, porcine primordial germ cells (PGCs) were isolated from gonads of 24- and 28-day embryos, and were then treated with BIO either individually or in combination with other cytokines (stem cell factor (SCF), leukemia inhibitory factor (LIF), and fibroblast growth factor (FGF); abbreviated as ‘3F’), and the effects of the treatment on the proliferation ability of porcine PGCs at early stage were examined using 5-bromo-2-deoxyuridine (Brdu) immunostaining assay. After continuous culture, the effects on the efficiency of porcine undifferentiated EG cells in the third passage and differentiated EG cells from embryoid bodies were examined as well. The results obtained through the observation of the Brdu-labeled PGCs indicated that BIO in combination with 3F resulted in a significant increase in the mitosis index, and also indicated that the BIO in combination with 3F had a higher efficiency in promoting the formation of porcine EG colony derived from porcine day 24 PGCs than BIO used either individually or in combination with LIF. In addition, BIO in combination with 3F exhibited the apparent anti-differentiation activity by reversing the differentiated EG cells to the undifferentiated status. Our results demonstrate that BIO in combination with SCF, LIF, and FGF could significantly contribute to the establishment of a porcine EG cell colony and maintain the undifferentiated status.

scholarly journals Leukemia Inhibitory Factor, Oncostatin M, IL-6, and Stem Cell Factor mRNA Expression in Human Thymus Increases with Age and Is Associated with Thymic Atrophy

2000 ◽  
Vol 164 (4) ◽  
pp. 2180-2187 ◽  
Author(s):  
Gregory D. Sempowski ◽  
Laura P. Hale ◽  
John S. Sundy ◽  
Janice M. Massey ◽  
Richard A. Koup ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mrna Expression ◽  
Leukemia Inhibitory Factor ◽  
Stem Cell Factor ◽  
Oncostatin M ◽  
Inhibitory Factor ◽  
Thymic Atrophy ◽  
Human Thymus

Hematologic effects of stem cell factor (SCF) and leukemia inhibitory factor (LIF) in vivo: LIF-induced thrombocytosis in SCF-primed mice

2009 ◽  
Vol 54 (4) ◽  
pp. 217-225 ◽  
Author(s):  
Thomas R. Ulich ◽  
Juan Castillo ◽  
Sung S. Shin ◽  
Songmei Yin ◽  
Diane Duryea ◽  
...  
Keyword(s):  
Stem Cell ◽  
Leukemia Inhibitory Factor ◽  
Stem Cell Factor ◽  
Inhibitory Factor

scholarly journals In vitro antioxidant treatment recovers proliferative responses of anergic CD4+ lymphocytes from human immunodeficiency virus-infected individuals

Blood ◽  
1996 ◽  
Vol 87 (11) ◽  
pp. 4746-4753 ◽  
Author(s):  
A Cayota ◽  
F Vuillier ◽  
G Gonzalez ◽  
G Dighiero
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Redox Status ◽  
Therapeutic Strategies ◽  
Antioxidant Treatment ◽  
Immunodeficiency Virus ◽  
Cd4 Lymphocytes ◽  
Cellular Thiol

Oxidative stress has been proposed to be involved in the immunologic defeat observed in effector calls of the immune system as well as in lymphocyte cell death and viral replication in human immunodeficiency virus (HIV)-infected patients. Because thiol-containing antioxidants such as N-acetyl-L-cysteine have been shown to have beneficial effects on CD4+ lymphocyte survival and to inhibit programmed cell death and HIV-1 replication, they may play a role in therapeutic strategies of this disease. In this work we have studied the cellular thiol levels and the affect of in vitro antioxidant treatment of purified CD4+ lymphocytes from HIV-infected patients, and correlated these parameters to proliferative responses and programmed cell death. We show that CD4+ lymphocytes from HIV-infected patients display impaired proliferative responses and a significant decrease in cellular thiol levels, indicating a disturbed redox status. Interestingly, antioxidant treatment succeeded to restore defective proliferative responses to CD3- mediated activation in 8 of 11 patients (high antioxidant responders). In contrast to high responders, patients failing to respond to antioxidant treatment (low antioxidant responders), were characterized by an abnormal ratio of apoptotic cells, which was not affected by N- acetyl-L-cysteine and/or 2-beta-mercaptoethanol preincubation. These results demonstrate for the first time that antioxidant treatment is able to revert the impaired proliferative activity of CD4 cells from HIV-infected patients and could help designing therapeutic strategies with antioxidant drugs. However, this action is not observed in cells undergoing programmed cell death.

Suppression of cell proliferation and programmed cell death by dexamethasone during postnatal lung development

2002 ◽  
Vol 282 (3) ◽  
pp. L477-L483 ◽  
Author(s):  
Cédric Luyet ◽  
Peter H. Burri ◽  
Johannes C. Schittny
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Lung Development ◽  
Structural Changes ◽  
Tissue Transglutaminase ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Morphological Criteria ◽  
Postnatal Lung Development

Prematurely born babies are often treated with glucocorticoids. We studied the consequences of an early postnatal and short dexamethasone treatment (0.1–0.01 μg/g, days 1–4) on lung development in rats, focusing on its influence on peaks of cell proliferation around day 4 and of programmed cell death at days 19–21. By morphological criteria, we observed a dexamethasone-induced premature maturation of the septa ( day 4), followed by a transient septal immatureness and delayed alveolarization leading to complete rescue of the structural changes. The numbers of proliferating (anti-Ki67) and dying cells (TdT-mediated dUTP nick end labeling) were determined and compared with controls. In dexamethasone-treated animals, both the peak of cell proliferation and the peak of programmed cell death were reduced to baseline, whereas the expression of tissue transglutaminase (transglutaminase-C), another marker for postnatal lung maturation, was not significantly altered. We hypothesize that a short neonatal course of dexamethasone leads to severe but transient structural changes of the lung parenchyma and influences the balance between cell proliferation and cell death even in later stages of lung maturation.

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