Apoptosis in the haemopoietic system

1994 ◽  
Vol 345 (1313) ◽  
pp. 257-263 ◽  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Cell Survival ◽  
Lineage Differentiation ◽  
Haemopoietic Stem Cells ◽  
Underlying Causes ◽  
Membrane Bound ◽  
Survival Signals

Our previous studies have shown that haemopoietic stem cells undergo apoptotic death as a consequence of growth factor withdrawal. In this paper we review the new data that has accumulated since this observation and compare it with older data from the ‘pre-apoptotic’ age. Models of erythropoiesis and granulopoiesis that incorporate apoptosis as a normal physiological process controlling homeostasis are examined. The converse to cell death is cell survival, and we describe experiments which suggest that haemopoietic growth factors can not only act as mitogenic or differentiation stimuli but also act as survival signals. We, and others, have proposed that these growth factor-induced survival signals act through the membrane bound polypeptide receptors and share common features of signal transduction with proliferative responses. Enforced expression of bcl-2 in haemopoietic stem cells is able to overcome apoptosis following the withdrawal of growth factor, and the cells commit into different lineage differentiation programmes. Such cells spontaneously differentiate without cell division, suggesting a stochastic model of haemopoiesis in which the major role of haemopoietic growth factors is to suppress apoptosis and act as mitogens. We review the evidence that the underlying causes of some haematological diseases may be associated with change in the balance between cell survival and death.

scholarly journals Regulation of Cell Growth

1987 ◽  
Vol 80 (9) ◽  
pp. 591-593
Author(s):  
A J Barrett
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cell Growth ◽  
Cell Lines ◽  
Growth Regulation ◽  
Platelet Derived Growth Factor ◽  
Haemopoietic Stem Cells

At this meeting of the RSM's Section of Pathology, the regulation of haemopoietic stem cells and growth factors regulating various cell lines were described, and the role of oncogenes, platelet-derived growth factor and nerve growth factor in growth regulation was discussed.

scholarly journals Maintenance of a Schwann-Like Phenotype in Differentiated Adipose-Derived Stem Cells Requires the Synergistic Action of Multiple Growth Factors

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Alice E. Mortimer ◽  
Alessandro Faroni ◽  
Mahmut A. Kilic ◽  
Adam J. Reid
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Growth Medium ◽  
Cell Morphology ◽  
Synergistic Action ◽  
Adipose Derived Stem Cells ◽  
Glial Growth Factor ◽  
Stimulating Factor

Differentiating human adipose-derived stem cells (ASCs) towards Schwann cells produces an unstable phenotype when stimulating factors are withdrawn. Here, we set out to examine the role of glial growth factor 2 (GGF-2) in the maintenance of Schwann-like cells. Following ASC differentiation to Schwann-like cells, stimulating factors were withdrawn such that cells either remained in media supplemented with all stimulating factors, GGF-2 alone, or underwent complete withdrawal of all factors. Furthermore, each stimulating factor was also removed from the growth medium individually. At 72 hours, gene (qRT-PCR) and protein (ELISA) expression of key Schwann cell factors were quantified and cell morphology was analysed. Cells treated with GGF-2 alone reverted to a stem cell morphology and did not stimulate the production of brain-derived neurotrophic factor (BDNF), regardless of the concentration of GGF-2 in the growth medium. However, GGF-2 alone increased the expression of Krox20, the main transcription factor involved in myelination, relative to those cells treated with all stimulating factors. Cells lacking fibroblast growth factor were unable to maintain a Schwann-like morphology, and those lacking forskolin exhibited a downregulation in BDNF production. Therefore, it is likely that the synergistic action of multiple growth factors is required to maintain Schwann-like phenotype in differentiated ASCs.

The role of growth factors in self-renewal and differentiation of haemopoietic stem cells

1990 ◽  
Vol 327 (1239) ◽  
pp. 85-98 ◽  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Growth Factors ◽  
Stromal Cells ◽  
Cell Lineage ◽  
Self Renewal ◽  
Haemopoietic Stem Cells

Haemopoietic stem cells in vivo proliferate and develop in association with stromal cells of the bone marrow. Proliferation and differentiation of haemopoietic stem cells also occurs in vitro , either in association with stromal cells or in response to soluble growth factors. Many of the growth factors that promote growth and development of haemopoietic cells in vitro have now been molecularly cloned and purified to homogeneity and various techniques have been described that allow enrichment (to near homogeneity) of multipotential stem cells. This in turn, has facilitated studies at the mechanistic level regarding the role of such growth factors in self-renewal and differentiation of stem cells and their relevance in stromal-cell mediated haemopoiesis. Our studies have shown that at least some multipotential cells express receptors for most, if not all, of the haemopoietic cell growth factors already characterized and that to elicit a response, several growth factors often need to be present at the same time. Furthermore, lineage development reflects the stimuli to which the cells are exposed, that is, some stimuli promote differentiation and development of multipotential cells into multiple cell lineages, whereas others promote development of multipotential cells into only one cell lineage. We suggest that, in the bone marrow environment, the stromal cells produce or sequester different types of growth factors, leading to the formation of microenvironments that direct cells along certain lineages. Furthermore, a model system has been used to show the possibility that the self-renewal probability of multipotential cells can also be modulated by the range and concentrations of growth factors present in the environment. This suggests that discrete microenvironments, preferentially promoting self-renewal rather than differentiation of multipotential cells, may also be provided by marrow stromal cells and sequestered growth factors.

scholarly journals Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Simona Ceccarelli ◽  
Cristina Nodale ◽  
Enrica Vescarelli ◽  
Paola Pontecorvi ◽  
Valeria Manganelli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Keratinocyte Growth Factor ◽  
Adipogenic Differentiation ◽  
Growth Factor Signaling ◽  
Adipose Derived Stem Cells ◽  
Transient Activation ◽  
Neuropilin 1

Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs.

Growth factors, stem cells, and stroke

2008 ◽  
Vol 24 (3-4) ◽  
pp. E14 ◽  
Author(s):  
Haviryaji S. G. Kalluri ◽  
Robert J. Dempsey
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Neural Stem Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Compensatory Mechanism ◽  
Ischemic Tissue ◽  
And Migration

✓ Postischemic neurogenesis has been identified as a compensatory mechanism to repair the damaged brain after stroke. Several factors are released by the ischemic tissue that are responsible for proliferation, differentiation, and migration of neural stem cells. An understanding of their roles may allow future therapies based on treatment with such factors. Although damaged cells release a variety of factors, some of them are stimulatory whereas some are inhibitory for neurogenesis. It is interesting to note that factors like insulin-like growth factor–I can induce proliferation in the presence of fibroblast growth factor–2 (FGF-2), and promote differentiation in the absence of FGF-2. Meanwhile, factors like transforming growth factor–β can induce the differentiation of neurons while inhibiting the proliferation of neural stem cells. Therefore, understanding the role of each factor in the process of neurogenesis will help physicians to enhance the endogenous response and improve the clinical outcome after stroke. In this article the authors discuss the role of growth factors and stem cells following stroke.

scholarly journals Unlike its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 192
Author(s):  
Siska Van Belle ◽  
Sara El Ashkar ◽  
Kateřina Čermáková ◽  
Filip Matthijssens ◽  
Steven Goossens ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Survival ◽  
Cell Lines ◽  
Protein Interactions ◽  
Leukemic Cell ◽  
Related Protein ◽  
Histone Tails ◽  
Knockout Mouse Model ◽  
Leukemic Cell Lines

HDGF-related protein 2 (HRP-2) is a member of the Hepatoma-Derived Growth Factor-related protein family that harbors the structured PWWP and Integrase Binding Domain, known to associate with methylated histone tails or cellular and viral proteins, respectively. Interestingly, HRP-2 is a paralog of Lens Epithelium Derived Growth Factor p75 (LEDGF/p75), which is essential for MLL-rearranged (MLL-r) leukemia but dispensable for hematopoiesis. Sequel to these findings, we investigated the role of HRP-2 in hematopoiesis and MLL-r leukemia. Protein interactions were investigated by co-immunoprecipitation and validated using recombinant proteins in NMR. A systemic knockout mouse model was used to study normal hematopoiesis and MLL-ENL transformation upon the different HRP-2 genotypes. The role of HRP-2 in MLL-r and other leukemic, human cell lines was evaluated by lentiviral-mediated miRNA targeting HRP-2. We demonstrate that MLL and HRP-2 interact through a conserved interface, although this interaction proved less dependent on menin than the MLL-LEDGF/p75 interaction. The systemic HRP-2 knockout mice only revealed an increase in neutrophils in the peripheral blood, whereas the depletion of HRP-2 in leukemic cell lines and transformed primary murine cells resulted in reduced colony formation independently of MLL-rearrangements. In contrast, primary murine HRP-2 knockout cells were efficiently transformed by the MLL-ENL fusion, indicating that HRP-2, unlike LEDGF/p75, is dispensable for the transformation of MLL-ENL leukemogenesis but important for leukemic cell survival.

scholarly journals Antiproliferative function of glia maturation factor beta.

1990 ◽  
Vol 1 (10) ◽  
pp. 741-746 ◽  
Author(s):  
R Lim ◽  
W X Zhong ◽  
A Zaheer
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Target Cell ◽  
G1 Phase ◽  
Glia Maturation Factor ◽  
Pituitary Extract ◽  
Mitogenic Effect ◽  
Maturation Factor ◽  
Cultured Astrocytes

Recombinant human glia maturation factor beta (GMF-beta) reversibly inhibits the proliferation of neoplastic cells in culture by arresting the cells in the G0/G1 phase. This phenomenon is not target-cell specific, as neural and nonneural cells are equally inhibited. When tested simultaneously, GMF-beta suppresses the mitogenic effect of acidic fibroblasts growth factor (aFGF), but the two are synergistic in promoting the morphologic differentiation of cultured astrocytes. GMF-beta also counteracts the growth-stimulating effect of pituitary extract and cholera toxin on Schwann cells. The results underscore the regulatory role of GMF-beta and its intricate interaction with the mitogenic growth factors.

scholarly journals The Role of Cellular Prion Protein in Cancer Biology: A Potential Therapeutic Target

2021 ◽  
Vol 11 ◽  
Author(s):  
Manqiu Ding ◽  
Yongqiang Chen ◽  
Yue Lang ◽  
Li Cui
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Cell Survival ◽  
Cancer Cells ◽  
Prion Protein ◽  
Therapeutic Target ◽  
Cancer Biology ◽  
Cellular Prion Protein ◽  
Potential Therapeutic Target

Prion protein has two isoforms including cellular prion protein (PrPC) and scrapie prion protein (PrPSc). PrPSc is the pathological aggregated form of prion protein and it plays an important role in neurodegenerative diseases. PrPC is a glycosylphosphatidylinositol (GPI)-anchored protein that can attach to a membrane. Its expression begins at embryogenesis and reaches the highest level in adulthood. PrPC is expressed in the neurons of the nervous system as well as other peripheral organs. Studies in recent years have disclosed the involvement of PrPC in various aspects of cancer biology. In this review, we provide an overview of the current understanding of the roles of PrPC in proliferation, cell survival, invasion/metastasis, and stem cells of cancer cells, as well as its role as a potential therapeutic target.

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