Role of stem cell factor in somatic–germ cell interactions during prenatal oogenesis

Zygote ◽  
1996 ◽  
Vol 4 (04) ◽  
pp. 349-351 ◽  
Author(s):  
Massimo De Felici ◽  
Anna Di Carlo ◽  
Maurizio Pesce
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Stem Cell Factor ◽  
Molecular Mechanisms ◽  
Primordial Germ Cells ◽  
Significant Progress ◽  
Proliferation And Differentiation ◽  
Complex Events ◽  
Mechanisms Of Migration

During embryogenesis germ cells originate from primordial germ cells (PGCs). The development of mammalian PGCs involves a number of complex events (formation and segregation of PGC precursors, PGC migration and proliferation) which lead to the differentiation of oocytes or prospermatogonia (for a review see De Feliciet al., 1992). During recent years developments in methods for isolation, purification and culture of mouse PGCs have led to significant progress in the understanding of molecular mechanisms of migration, proliferation and differentiation of these cells (for reviews see De Felici, 1994; and De Felici & Pesce, 1994a). In this paper we describe the key role played by stem cell factor (SCF) in PGC development and early folliculogenesis.

scholarly journals TET2 deficiency leads to stem cell factor–dependent clonal expansion of dysfunctional erythroid progenitors

Blood ◽  
2018 ◽  
Vol 132 (22) ◽  
pp. 2406-2417 ◽  
Author(s):  
Xiaoli Qu ◽  
Shijie Zhang ◽  
Shihui Wang ◽  
Yaomei Wang ◽  
Wei Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Molecular Mechanisms ◽  
Erythroid Differentiation ◽  
Negative Regulator ◽  
Loss Of Function ◽  
Erythroid Progenitors ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation

Abstract Myelodysplastic syndromes (MDSs) are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis. Anemia is the defining cytopenia of MDS patients, yet the molecular mechanisms for dyserythropoiesis in MDSs remain to be fully defined. Recent studies have revealed that heterozygous loss-of-function mutation of DNA dioxygenase TET2 is 1 of the most common mutations in MDSs and that TET2 deficiency disturbs erythroid differentiation. However, mechanistic insights into the role of TET2 on disordered erythropoiesis are not fully defined. Here, we show that TET2 deficiency leads initially to stem cell factor (SCF)–dependent hyperproliferation and impaired differentiation of human colony-forming unit–erythroid (CFU-E) cells, which were reversed by a c-Kit inhibitor. We further show that this was due to increased phosphorylation of c-Kit accompanied by decreased expression of phosphatase SHP-1, a negative regulator of c-Kit. At later stages, TET2 deficiency led to an accumulation of a progenitor population, which expressed surface markers characteristic of normal CFU-E cells but were functionally different. In contrast to normal CFU-E cells that require only erythropoietin (EPO) for proliferation, these abnormal progenitors required SCF and EPO and exhibited impaired differentiation. We termed this population of progenitors “marker CFU-E” cells. We further show that AXL expression was increased in marker CFU-E cells and that the increased AXL expression led to increased activation of AKT and ERK. Moreover, the altered proliferation and differentiation of marker CFU-E cells were partially rescued by an AXL inhibitor. Our findings document an important role for TET2 in erythropoiesis and have uncovered previously unknown mechanisms by which deficiency of TET2 contributes to ineffective erythropoiesis.

Stem cell factor protects germ cells from apoptosis in vitro

2000 ◽  
Vol 113 (1) ◽  
pp. 161-168 ◽  
Author(s):  
W. Yan ◽  
J. Suominen ◽  
J. Toppari
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Stem Cell Factor ◽  
Primordial Germ Cells ◽  
Survival Function ◽  
Seminiferous Tubules ◽  
Testicular Development ◽  
Dna Laddering ◽  
Survival Effect

Stem cell factor (SCF) plays an important role in migration, adhesion, proliferation, and survival of primordial germ cells and spermatogonia during testicular development. However, the function of SCF in the adult testis is poorly described. We have previously shown that, in the presence of SCF, there were more type A spermatogonia incorporating thymidine at stage XII of rat seminiferous tubules cultured in vitro than in the absence of SCF, implying that the increased DNA synthesis might result from enhanced survival of spermatogonia. To explore the potential pro-survival function of SCF during spermatogenesis, the seminiferous tubules from stage XII were cultured in the presence or absence of SCF (100 ng/ml) for 8, 24, 48, and 72 hours, respectively, and apoptosis was analyzed by DNA laddering and in situ 3′-end labeling (ISEL) staining. Surprisingly, not only spermatogonia, but also spermatocytes and spermatids, were protected from apoptosis in the presence of SCF. Apoptosis took place much later and was less severe in the SCF-treated tubules than in the controls. Based on previous studies showing that FSH prevents germ cells from undergoing apoptosis in vitro, and that SCF level is increased dramatically in response to FSH stimulation, we also tested if the pro-survival effect of FSH is mediated through SCF by using a function-blocking monoclonal antibody, ACK-2, to block SCF/c-kit interaction. After 24 hours of blockade, the protective effect of FSH was partially abolished, as manifested by DNA laddering and ISEL analyses. The present study demonstrates that SCF acts as an important survival factor for germ cells in the adult rat testis and FSH pro-survival effect on germ cells is mediated partially through the SCF/c-kit pathway.

Primary culture of porcine PGCs requires LIF and porcine membrane-bound stem cell factor

Zygote ◽  
1998 ◽  
Vol 6 (3) ◽  
pp. 271-275 ◽  
Author(s):  
Gabriela Durcova-Hills ◽  
Katja Prelle ◽  
Sigrid Müller ◽  
Miodrag Stojkovic ◽  
Jan Motlik ◽  
...  
Keyword(s):  
Stem Cell ◽  
Primary Culture ◽  
Germ Cells ◽  
Stem Cell Factor ◽  
Primordial Germ Cells ◽  
Embryonic Stem ◽  
Leukaemia Inhibitory Factor ◽  
Feeder Cells ◽  
Membrane Bound

We studied the effect of murine leukaemia inhibitory factor (LIF), human basic fibroblast growth factor (bFGF) and porcine stem cell factor (SCF) on the survival and/or proliferation of porcine primordial germ cells (PGCs) obtained from 27-day-old embryos in vitro. PGCs were cultured in embryonic stem cell (ESC) medium supplemented with or without either LIF (1000 IU/ml) alone or LIF together with bFGF (10 ng/ml). They were seeded on mitotically inactivated feeder cells, either STO or transfected STO cells (STO#8), expressing the membrane-bound form of porcine SCF. PGCs were identified by their alkaline phosphatase (AP) activity and counted after 1, 3 and 5 days in culture. After 1 day of culture, PGCs cultured on STO#8 cells showed significantly higher survival than PGCs cultured on STO cells (p < 0.05). The combined effect of SCF and LIF caused a significant increase in PGC number by day 3 of culture when PGCs were cultured on either STO cells (p < 0.01) or STO#8 (p < 0.001). When SCF and LIF were used together with bFGF no increase in the PGC number was observed. Our results suggest that the membrane-bound form of porcine SCF plays a pivotal role in the primary culture of porcine PGCs and that bFGF is not required in vitro.

scholarly journals The Role of MicroRNAs in Cardiac Stem Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Nima Purvis ◽  
Andrew Bahn ◽  
Rajesh Katare
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Cardiac Stem Cells ◽  
Cell Therapies ◽  
Small Noncoding Rna ◽  
Proliferation And Differentiation

Stem cells are considered as the next generation drug treatment in patients with cardiovascular disease who are resistant to conventional treatment. Among several stem cells used in the clinical setting, cardiac stem cells (CSCs) which reside in the myocardium and epicardium of the heart have been shown to be an effective option for the source of stem cells. In normal circumstances, CSCs primarily function as a cell store to replace the physiologically depleted cardiovascular cells, while under the diseased condition they have been shown to experimentally regenerate the diseased myocardium. In spite of their major functional role, molecular mechanisms regulating the CSCs proliferation and differentiation are still unknown. MicroRNAs (miRs) are small, noncoding RNA molecules that regulate gene expression at the posttranscriptional level. Recent studies have demonstrated the important role of miRs in regulating stem cell proliferation and differentiation, as well as other physiological and pathological processes related to stem cell function. This review summarises the current understanding of the role of miRs in CSCs. A deeper understanding of the mechanisms by which miRs regulate CSCs may lead to advances in the mode of stem cell therapies for the treatment of cardiovascular diseases.

Stem Cell Factor Regulation of Apoptosis in Mouse Primordial Germ Cells

1997 ◽  
pp. 19-31 ◽  
Author(s):  
Maurizio Pesce ◽  
Maria Grazia Farrace ◽  
Alessandra Amendola ◽  
Mauro Piacentini ◽  
Massimo De Felici
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Stem Cell Factor ◽  
Primordial Germ Cells

Stem cell factor activates telomerase in mouse mitotic spermatogonia and in primordial germ cells

2002 ◽  
Vol 115 (8) ◽  
pp. 1643-1649
Author(s):  
Susanna Dolci ◽  
Lauretta Levati ◽  
Manuela Pellegrini ◽  
Isabella Faraoni ◽  
Grazia Graziani ◽  
...  
Keyword(s):  
Germ Cells ◽  
Stem Cell Factor ◽  
Primordial Germ Cells ◽  
Telomerase Activity ◽  
The Self ◽  
Mrna Levels ◽  
Male Germ Cells ◽  
Pi3k Inhibitor Ly294002 ◽  
Low Levels

The discovery of sterility in the descendants of telomerasenull mutant mice, owing to the lack of spermatogonia proliferation, has drawn attention to the role of telomerase activity in mouse spermatogenesis. Since spermatogonia proliferation is under Kitl control, we explored its possible role in the regulation of telomerase activity. We show that Kitl induces telomerase activity in mitotic spermatogonia and increases the mRNA levels of both the catalytic subunit form and the telomerase RNA template. The increase of telomerase activity by Kitl is blocked by the presence of the PI3K inhibitor LY294002. Kit-positive proliferating male primordial germ cells (PGCs) show low levels of telomerase activity, but they increase telomerase activity upon Kitl stimulation. Diplotene-arrested growing oocytes that reexpress Kit do not increase telomerase activity upon Kitl stimulation. Our data suggest that the induction of telomerase by Kitl may contribute to the self-renewing potential of male germ cells and of PGCs.

Stem cell factor and c-Kit in human primordial germ cells and fetal ovaries

2005 ◽  
Vol 234 (1-2) ◽  
pp. 1-10 ◽  
Author(s):  
Poul Erik Høyer ◽  
Anne Grete Byskov ◽  
Kjeld Møllgård
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Stem Cell Factor ◽  
Primordial Germ Cells
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