Leukaemia inhibitory factor stimulates proliferation of prospermatogonial stem cells

1997 ◽  
Vol 9 (7) ◽  
pp. 717 ◽  
Author(s):  
Diana B. Nikolova ◽  
Yordanka S. Martinova ◽  
Martin Seidensticker ◽  
Anthony R. Bellvé
Keyword(s):  
Stem Cells ◽  
Germ Cells ◽  
Proliferative Activity ◽  
Inhibitory Factor ◽  
Leukaemia Inhibitory Factor ◽  
Synthetic Activity ◽  
Local Regulation ◽  
Rat Testis ◽  
A Cell ◽  
Stimulation Of

The effect of leukaemia inhibitory factor (LIF) on the proliferation of prospermatogonial stem cells was testedin vitro. Pieces of 3-day-old rat testis were cultured in the presence of a range of doses of LIF alone or in combination with 1 ng mL -1 seminiferous growth factor (SGF). Stimulation of the proliferative activity of quiescent prospermatogonia was detected immunocytochemically with a cell proliferation kit. After 24 h culture, LIF signicantly increased the percentage of labelled prospermatogonia, with the peak of activity at 20 pg mL -1 . The combination of LIF and SGF resulted in a decrease in DNA synthetic activity of the germ cells. Hence, LIF and SGF play a role in local regulation at the onset of spermatogenesis in the rat testis.

scholarly journals Function of leukaemia inhibitory factor in spermatogenesis of a teleost fish, the medaka Oryzias latipes

Zygote ◽  
2019 ◽  
Vol 27 (6) ◽  
pp. 423-431 ◽  
Author(s):  
Ryuichi Satoh ◽  
Hisanori Bando ◽  
Noriyoshi Sakai ◽  
Tomoya Kotani ◽  
Masakane Yamashita
Keyword(s):  
Stem Cells ◽  
Primordial Germ Cells ◽  
Embryonic Stem ◽  
Inhibitory Factor ◽  
Leukaemia Inhibitory Factor ◽  
Hormonal Stimulation ◽  
A Cell ◽  
Established Cell

SummaryIn response to gonadotropins and androgens, testicular cells produce various molecules that control proper proliferation and differentiation of spermatogenic cells through their paracrine and autocrine actions. However, molecules functioning downstream of the hormonal stimulation are poorly understood. Leukaemia inhibitory factor (Lif) is known to maintain the pluripotency of stem cells including embryonic stem cells and primordial germ cells at least in vitro, but its actual roles in vivo remain to be elucidated. To clarify the function of Lif in teleost (medaka) testes, we examined the effects of Lif on spermatogenesis in a newly established cell culture system using a cell line (named Mtp1) derived from medaka testicular somatic cells as feeder cells. We found that addition of baculovirus-produced recombinant medaka Lif to the culture medium or co-culture with Lif-overexpressing Mtp1 cells increased the number of spermatogonia. In situ hybridization and immunohistochemical analyses of the medaka testes showed that mRNAs and proteins of Lif are expressed in spermatogonia and the surrounding Sertoli cells, with higher expression levels in type A (undifferentiated) spermatogonia than in type B (differentiated) spermatogonia. Our findings suggest that Lif regulates spermatogonial cell proliferation in the medaka.

scholarly journals Leukaemia Inhibitory Factor (LIF) Inhibits Cancer Stem Cells Tumorigenic Properties through Hippo Kinases Activation in Gastric Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2011
Author(s):  
Lornella Seeneevassen ◽  
Julie Giraud ◽  
Silvia Molina-Castro ◽  
Elodie Sifré ◽  
Camille Tiffon ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Lines ◽  
Kinase Inhibitor ◽  
Hippo Pathway ◽  
Resistance Mechanisms ◽  
Inhibitory Factor ◽  
Nuclear Accumulation ◽  
Leukaemia Inhibitory Factor

Cancer stem cells (CSCs) present chemo-resistance mechanisms contributing to tumour maintenance and recurrence, making their targeting of utmost importance in gastric cancer (GC) therapy. The Hippo pathway has been implicated in gastric CSC properties and was shown to be regulated by leukaemia inhibitory factor receptor (LIFR) and its ligand LIF in breast cancer. This study aimed to determine LIF’s effect on CSC properties in GC cell lines and patient-derived xenograft (PDX) cells, which remains unexplored. LIF’s treatment effect on CSC markers expression and tumoursphere formation was evaluated. The Hippo kinase inhibitor XMU-MP-1 and/or the JAK1 inhibitor Ruxolitinib were used to determine Hippo and canonical JAK/STAT pathway involvement in gastric CSCs’ response to LIF. Results indicate that LIF decreased tumorigenic and chemo-resistant CSCs, in both GC cell lines and PDX cells. In addition, LIF increased activation of LATS1/2 Hippo kinases, thereby decreasing downstream YAP/TAZ nuclear accumulation and TEAD transcriptional activity. LIF’s anti-CSC effect was reversed by XMU-MP-1 but not by Ruxolitinib treatment, highlighting the opposite effects of these two pathways downstream LIFR. In conclusion, LIF displays anti-CSC properties in GC, through Hippo kinases activation, and could in fine constitute a new CSCs-targeting strategy to help decrease relapse cases and bad prognosis in GC.

scholarly journals Regulation of embryonic stem cell self-renewal and pluripotency by leukaemia inhibitory factor

2011 ◽  
Vol 438 (1) ◽  
pp. 11-23 ◽  
Author(s):  
Hiroyuki Hirai ◽  
Peter Karian ◽  
Nobuaki Kikyo
Keyword(s):  
Stem Cells ◽  
Embryonic Stem ◽  
Gene Expression Pattern ◽  
Receptor Activation ◽  
Janus Kinase ◽  
Inhibitory Factor ◽  
Mitogen Activated Protein Kinase ◽  
Leukaemia Inhibitory Factor ◽  
Signalling Pathways ◽  
Self Renewal

LIF (leukaemia inhibitory factor) is a key cytokine for maintaining self-renewal and pluripotency of mESCs (mouse embryonic stem cells). Upon binding to the LIF receptor, LIF activates three major intracellular signalling pathways: the JAK (Janus kinase)/STAT3 (signal transducer and activator of transcription 3), PI3K (phosphoinositide 3-kinase)/AKT and SHP2 [SH2 (Src homology 2) domain-containing tyrosine phosphatase 2]/MAPK (mitogen-activated protein kinase) pathways. These pathways converge to orchestrate the gene expression pattern specific to mESCs. Among the many signalling events downstream of the LIF receptor, activation and DNA binding of the transcription factor STAT3 plays a central role in transducing LIF's functions. The fundamental role of LIF for pluripotency was highlighted further by the discovery that LIF accelerates the conversion of epiblast-derived stem cells into a more fully pluripotent state. In the present review, we provide an overview of the three major LIF signalling pathways, the molecules that interact with STAT3 and the current interpretations of the roles of LIF in pluripotency.

Effect of Steel factor and leukaemia inhibitory factor on murine primordial germ cells in culture

Nature ◽  
1991 ◽  
Vol 353 (6346) ◽  
pp. 750-752 ◽  
Author(s):  
Yasuhisa Matsui ◽  
Deniz Toksoz ◽  
Satomi Nishikawa ◽  
Shin-Ichi Nishikawa ◽  
David Williams ◽  
...  
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells ◽  
Inhibitory Factor ◽  
Leukaemia Inhibitory Factor ◽  
Steel Factor ◽  
Cells In Culture

Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells

Nature ◽  
1988 ◽  
Vol 336 (6200) ◽  
pp. 684-687 ◽  
Author(s):  
R. Lindsay Williams ◽  
Douglas J. Hilton ◽  
Shirley Pease ◽  
Tracy A. Willson ◽  
Colin L. Stewart ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Myeloid Leukaemia ◽  
Embryonic Stem ◽  
Inhibitory Factor ◽  
Leukaemia Inhibitory Factor ◽  
Developmental Potential

scholarly journals Axotrophin and leukaemia inhibitory factor (LIF) in transplantation tolerance

2005 ◽  
Vol 360 (1461) ◽  
pp. 1687-1694 ◽  
Author(s):  
Su M Metcalfe
Keyword(s):  
Stem Cells ◽  
Treg Cells ◽  
Inhibitory Factor ◽  
Leukaemia Inhibitory Factor ◽  
Transplantation Tolerance ◽  
Immune Effector ◽  
Effector Cells ◽  
Regulatory Pathways ◽  
Draining Lymph Node

Immune self-tolerance is controlled by a subset of T lymphocytes that are regulatory (Treg) and epigenetically programmed to suppress auto-reactive immune effector cells in vivo . By extrapolation, donor-specific transplantation tolerance might be controlled by donor-specific Treg that have acquired the appropriate epigenetic program for tolerance. Although such tolerance has yet to be achieved in man, proof of concept comes from mouse models where regulatory transplantation tolerance can be induced within the complex micro-environment of the spleen or draining lymph node. By studying whole spleen cell populations in a murine model of transplantation tolerance we have incorporated a complexity of environmental factors when looking for specific features that characterize tolerance versus aggression. This approach has revealed unexpected patterns of gene activity in tolerance and most notably that a novel stem cell gene, axotrophin , regulates T lymphocyte responsiveness both in terms of proliferation and in release of leukaemia inhibitory factor (LIF). Since LIF is a regulator of stem cells in addition to being a key neuropoietic cytokine, these preliminary results linking both axotrophin and LIF to transplantation tolerance lead us to propose that regulatory pathways encoded during the epigenetic development of Treg cells are related to pathways that regulate fate determination of stem cells.

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