scholarly journals Signaling Pathways in Mouse Embryo Stem Cell Self-Renewal

10.5772/22933 ◽  
2011 ◽  
Author(s):  
Leo Quinlan
Keyword(s):  
Stem Cell ◽  
Signaling Pathways ◽  
Mouse Embryo ◽  
Self Renewal

Signaling pathways influencing stem cell self-renewal and differentiation—Special emphasis on cardiomyocytes

2021 ◽  
pp. 157-168
Author(s):  
Selvaraj Jayaraman ◽  
Ponnulakshmi Rajagopal ◽  
Vijayalakshmi Periyasamy ◽  
Kanagaraj Palaniyandi ◽  
R. Ileng Kumaran ◽  
...  
Keyword(s):  
Stem Cell ◽  
Signaling Pathways ◽  
Self Renewal

Lnk Controls Hematopoietic Stem Cell Self-Renewal through Direct Interactions with JAK2 and Contributes to Oncogenic JAK2-Induced Myeloproliferative Diseases in Mice

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 895-895
Author(s):  
Alexey Bersenev ◽  
Chao Wu ◽  
Joanna Balcerek ◽  
Wei Tong
Keyword(s):  
Stem Cell ◽  
Signaling Pathways ◽  
Hematopoietic Stem Cell ◽  
Adaptor Protein ◽  
Janus Kinase ◽  
Myelogenous Leukemia ◽  
Cell Surface Receptor ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Myeloproliferative Diseases

Abstract Hematopoietic stem cell (HSC) homeostasis and self-renewal are regulated by intrinsic cytokine signaling pathways. One important signaling axis for HSC is the cell surface receptor, Mpl, and its ligand, thrombopoietin (Tpo). Upon Tpo stimulation, Mpl activates Janus Kinase (JAK2) that triggers a cascade of downstream signal transduction pathways that regulates many aspects of cell development. Under steady-state conditions, mice lacking the inhibitory adaptor protein Lnk harbor an expanded HSC pool with enhanced self-renewal. Surprisingly, we found that Lnk−/− HSCs have an increased quiescent fraction, decelerated cell cycle kinetics, and enhanced resistance to repeated 5-Florouracil (5-FU) treatments in vivo compared to wild type HSCs. We further provided genetic evidence demonstrating that Lnk controls HSC quiescence and self-renewal predominantly through Mpl. Consistent with this observation, Lnk deficiency in HSCs potentiates JAK2 activation in response to TPO. Biochemical experiments reveal that Lnk directly binds to phosphorylated tyrosine residues in JAK2 following TPO stimulation. Dysregulation of cytokine receptor signaling pathways leads to hematological malignancies. Abnormal activation of JAK2 by a chromosomal translocation between the transcription factor Tel and JAK2 (Tel/JAK2) was shown to cause atypical Chronic Myelogenous Leukemia (aCML). Recently, the JAK2 V617F mutation has been observed at high frequencies in several myeloproliferative diseases (MPDs). The JAK2V617F mutant retains Lnk binding ability, suggesting Lnk status could modify MPD development. Indeed, we found that loss of Lnk accelerates oncogenic JAK2- induced CML/MPD in the mouse transplant models. Therefore, we identified Lnk as a physiological negative regulator of JAK2 in stem cells that may contribute to leukemic transformation conferred by oncogenic JAK2.

Transcription Factor Integration from Pathways Regulating Adult Blood Stem Cell Production and Self-Renewal.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. sci-14-sci-14
Author(s):  
Leonard I. Zon
Keyword(s):  
Stem Cell ◽  
Signaling Pathways ◽  
Binding Sites ◽  
Wnt Pathway ◽  
Dominant Negative ◽  
Transgenic Zebrafish ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Transcriptional Output ◽  
Multiple Signaling

Self-renewal of hematopoietic stem cells (HSCs) involves multiple signaling and transcription factors. We recently showed that prostaglandin (PG) E2 regulates the induction and engraftment of vertebrate HSC pathways. Yet, the targets and transcriptional output of the PGE2 pathway remains to be defined. The wnt pathway similarly affects HSC formation; activation of wnt signaling in heat-shock inducible transgenic zebrafish led to enhanced HSC formation, while inhibition of wnt/β-catenin signaling at the membrane level (dickkopf), in the cytosol (axin) or in the nucleus (dominant negative TCF), reduced HSC numbers. Using wnt transcriptional reporter zebrafish with multimerized TCF-binding sites. PGE2 was found to increase activity during embryonic development, demonstrating a direct interaction between these signaling pathways. The transcriptional output of the wnt pathway is linked to the interaction of TCF with β-catenin. Based on the transcriptional increase in multimerized TCF binding sites in vivo, we had hypothesized that prostaglandin signaling directly stimulates β-catenin activation. β-catenin is known to be phosphorylated on critical residues that modulate its activity. In marrow-derived cells, we demonstrate that prostaglandin increases a cyclic AMP pathway that leads to the PKA phosphorylation of β-catenin, thereby increasing its transcriptional activity. In HSCs, the interaction of multiple signaling pathways with transcriptional output is a method for modulating self-renewal in the stem cell pool as well as tissue differentiation.

scholarly journals Wnt/β-catenin and LIF–Stat3 signaling pathways converge on Sp5 to promote mouse embryonic stem cell self-renewal

2015 ◽  
Vol 129 (2) ◽  
pp. 269-276 ◽  
Author(s):  
Shoudong Ye ◽  
Dongming Zhang ◽  
Fei Cheng ◽  
Daniel Wilson ◽  
Jeffrey Mackay ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Signaling Pathways ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Self Renewal ◽  
Stat3 Signaling

scholarly journals Abnormal Glycosylation of Cancer Stem Cells and Targeting Strategies

2021 ◽  
Vol 11 ◽  
Author(s):  
Thahomina Khan ◽  
Horacio Cabral
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Self Renewal ◽  
Tumor Relapse ◽  
Intracellular Signaling Pathways ◽  
Abnormal Glycosylation

Cancer stem cell (CSCs) are deemed as one of the main reasons of tumor relapse due to their resistance to standard therapies. Numerous intracellular signaling pathways along with extracellular features are crucial in regulating CSCs properties, such as heterogeneity, plasticity and differentiation. Aberrant glycosylation of these cellular signaling pathways and markers of CSCs have been directly correlated with maintaining survival, self-renewal and extravasation properties. In this review, we highlight the importance of glycosylation in promoting stemness character of CSCs, and present strategies for targeting abnormal glycosylation to eliminate the resistant CSC population.

Wnt/β-catenin and LIF–Stat3 signaling pathways converge on Sp5 to promote mouse embryonic stem cell self-renewal

Development ◽  
2016 ◽  
Vol 143 (3) ◽  
pp. e1.1-e1.1
Author(s):  
Shoudong Ye ◽  
Dongming Zhang ◽  
Fei Cheng ◽  
Daniel Wilson ◽  
Jeffrey Mackay ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Signaling Pathways ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Self Renewal ◽  
Stat3 Signaling

Pleiotrophin Signaling Is Necessary and Sufficient for Hematopoietic Stem Cell Self-Renewal In Vivo

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 404-404 ◽  
Author(s):  
Heather A Himburg ◽  
Pamela Daher ◽  
J. Lauren Russell ◽  
Phuong Doan ◽  
Mamle Quarmyne ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Signaling Pathways ◽  
Fold Increase ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Human Hscs ◽  
Necessary And Sufficient

Abstract Abstract 404 Several signaling pathways have been elucidated which regulate hematopoietic stem cell self-renewal, including the Notch, Wnt, HOX and BMP signaling pathways. However, several of these pathways (e.g. Notch, Wnt) may not be necessary for maintenance of HSCs in vivo. We recently demonstrated that treatment of murine and human HSCs with the heparin binding growth factor, pleiotrophin (PTN), was sufficient to induce self-renewal of murine and human HSCs in culture (Himburg, Nat Med, 2010). In order to determine if PTN signaling is necessary for HSC self renewal and normal hematopoiesis in vivo, we examined the bone marrow HSC content and hematopoietic profile of mice bearing a constitutive deletion of PTN (PTN−/− mice) as well as mice bearing constitutive deletion of the PTN receptor, receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ) (courtesy of Dr. Gonzalo Herradon, Spain and Dr. Sheila Harroch, L'Institut Pasteur, Paris, FR). PTN−/− mice demonstrated no significant differences in total bone marrow (BM) cells or BM colony forming cells (CFCs) but had significantly decreased bone marrow CD34(-)c-kit(+)sca-1(+)lin(-) (34-KSL) cells compared to littermate controls which retained PTN (PTN+/+) mice (0.007% vs. 0.02%, p=0.03). Consistent with this phenotype, PTN−/− mice also contained 2–fold decreased CFU-S12 compared to control PTN+/+ mice (p= 0.003). PTN−/− mice also demonstrated an 11-fold reduction in long-term repopulating HSC content compared to PTN+/+ mice as measured via competitive repopulating assay (12 week CRU frequency: 1 in 6 cells vs. 1 in 66 cells). Taken together, these data demonstrate that PTN signaling is necessary for maintenance of the BM HSC pool in vivo. Since PTN is known to antagonize the phosphatase activity of RPTPβ/ζ, we hypothesized that deletion of RPTPβ/ζ would increase BM HSC self-renewal and result in expansion of the BM HSC pool in vivo. Consistent with this hypothesis, RPTPβ/ζ−/− mice displayed a 1.3-fold increase in total BM cells (p= 0.04), 1.8-fold increase in BM 34-KSL cells (p=0.03), 1.6-fold increase in BM CFCs (p= 0.002) and 1.6–fold increase in BM CFU-S (p< 0.0001). RPTPβ/ζ−/− mice also demonstrated 1.4–fold higher long-term repopulating capacity (12 weeks) following competitive repopulating assay compared to RPTPβ/ζ+/+ mice (Donor CD45.1+ cell engraftment: 4.2% vs. 1.5%). Interestingly, RPTPβ/ζ −/− mice had significantly increased PB white blood cell counts, hemoglobin and platelet counts compared to RPTPβ/ζ+/+ mice coupled with splenomegaly. The RPTPβ/ζ−/− mice also had significantly increased BM vascular density (via quantitative mouse endothelial cell antigen staining) compared to RPTPβ/ζ+/+ mice, suggesting that PTN/RPTPβ/ζ signaling may augment the HSC pool size directly and also indirectly via activation of the BM vascular niche. These results demonstrate that PTN signaling is necessary and sufficient for induction of HSC self-renewal in vivo. Disclosures: No relevant conflicts of interest to declare.

Signaling pathways governing stem-cell fate

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 492-503 ◽  
Author(s):  
Ulrika Blank ◽  
Göran Karlsson ◽  
Stefan Karlsson
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Signaling Pathways ◽  
Cell Fate ◽  
Cell Biology ◽  
Adult Stem Cell ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Recent Developments ◽  
Molecular Machinery

Hematopoietic stem cells (HSCs) are historically the most thoroughly characterized type of adult stem cell, and the hematopoietic system has served as a principal model structure of stem-cell biology for several decades. However, paradoxically, although HSCs can be defined by function and even purified to near-homogeneity, the intricate molecular machinery and the signaling mechanisms regulating fate events, such as self-renewal and differentiation, have remained elusive. Recently, several developmentally conserved signaling pathways have emerged as important control devices of HSC fate, including Notch, Wingless-type (Wnt), Sonic hedgehog (Shh), and Smad pathways. HSCs reside in a complex environment in the bone marrow, providing a niche that optimally balances signals that control self-renewal and differentiation. These signaling circuits provide a valuable structure for our understanding of how HSC regulation occurs, concomitantly with providing information of how the bone marrow microenvironment couples and integrates extrinsic with intrinsic HSC fate determinants. It is the focus of this review to highlight some of the most recent developments concerning signaling pathways governing HSC fate.

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