scholarly journals SHP2-Mediated Signal Networks in Stem Cell Homeostasis and Dysfunction

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Chen Kan ◽  
Fan Yang ◽  
Siying Wang

Stem cells, including embryonic stem cells (ESCs) and adult stem cells, play a central role in mammal organism development and homeostasis. They have two unique properties: the capacity for self-renewal and the ability to differentiate into many specialized cell types. Src homology region 2- (SH2-) containing protein tyrosine phosphatase 2 (SHP-2), a nonreceptor protein tyrosine phosphatase encoded by protein tyrosine phosphatase nonreceptor type 11 gene (PTPN11), regulates multicellular differentiation, proliferation, and survival through numerous conserved signal pathways. Gain-of-function (GOF) or loss-of-function (LOF) SHP2 in various cells, especially for stem cells, disrupt organism self-balance and lead to a plethora of diseases, such as cancer, maldevelopment, and excessive hyperblastosis. However, the exact mechanisms of SHP2 dysfunction in stem cells remain unclear. In this review, we intended to raise the attention and clarify the framework of SHP2-mediated signal pathways in various stem cells. Establishment of integrated signal architecture, from ESCs to adult stem cells, will help us to understand the changes of dynamic, multilayered pathways in response to SHP2 dysfunction. Overall, better understanding the functions of SHP2 in stem cells provides a new avenue to treat SHP2-associated diseases.

2016 ◽  
Vol 425 (1-2) ◽  
pp. 95-102
Author(s):  
Zahra Shokati Eshkiki ◽  
Mohammad Hossein Ghahremani ◽  
Parisa Shabani ◽  
Sattar Gorgani Firuzjaee ◽  
Asie Sadeghi ◽  
...  

1996 ◽  
Vol 91 (2) ◽  
pp. 304-307 ◽  
Author(s):  
Wouter G. van Inzen ◽  
Maikel P. Peppelenbosch ◽  
Maria W.M. van den Brand ◽  
Leon G.J. Tertoolen ◽  
Siegfried de Laat

Author(s):  
Stamatiki Katraki-Pavlou ◽  
Pinelopi Kastana ◽  
Dimitris Bousis ◽  
Despoina Ntenekou ◽  
Aimilia Varela ◽  
...  

Protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) is a transmembrane tyrosine phosphatase receptor highly expressed in embryonic stem cells. In the present work, gene expression analyses of Ptprz1-/- and Ptprz1+/+ mice endothelial cells and hearts pointed to an unidentified role of PTPRZ1 in heart development through regulation of heart-specific transcription factor genes. Echocardiography analysis in mice identified that both systolic and diastolic functions are affected in Ptprz1-/- compared to Ptprz1+/+ hearts, based on a dilated LV cavity, decreased ejection fraction and fraction shortening, and increased angiogenesis in Ptprz1-/- hearts, with no signs of cardiac hypertrophy. A zebrafish ptprz1-/- knockout was also generated and exhibits mis-regulated expression of developmental cardiac markers, bradycardia and defective heart morphogenesis characterized by enlarged ventricles and defected contractility. A selective PTPRZ1 tyrosine phosphatase inhibitor affected zebrafish heart development and function in a way like what is observed in the ptprz1-/- zebrafish. The same inhibitor had no effect in the function of the adult zebrafish heart, suggesting that PTPRZ1 is not important for the adult heart function, in line with data from the human cell atlas showing very low to negligible PTPRZ1 expression in the adult human heart. However, in line with the animal models, Ptprz1 was expressed in many different cell types in the human fetal heart, such as valvar, fibroblast-like, cardiomyocytes and endothelial cells. Collectively, these data suggest that PTPRZ1 regulates cardiac morphogenesis in a way that subsequently affects heart function and warrant further studies for the involvement of PTPRZ1 in idiopathic congenital cardiac pathologies.


Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2157-2165 ◽  
Author(s):  
Xinqiang Huang ◽  
Eric Gschweng ◽  
Ben Van Handel ◽  
Donghui Cheng ◽  
Hanna K. A. Mikkola ◽  
...  

Abstract MicroRNAs (miRs) play an important role in cell differentiation and maintenance of cell identity, but relatively little is known of their functional role in modulating human hematopoietic lineage differentiation. Human embryonic stem cells (hESCs) provide a model system to study early human hematopoiesis. We differentiated hESCs by embryoid body (EB) formation and compared the miR expression profile of undifferentiated hESCs to CD34+ EB cells. miRs-126/126* were the most enriched of the 7 miRs that were up-regulated in CD34+ cells, and their expression paralleled the kinetics of hematopoietic transcription factors RUNX1, SCL, and PU.1. To define the role of miRs-126/126* in hematopoiesis, we created hESCs overexpressing doxycycline-regulated miRs-126/126* and analyzed their hematopoietic differentiation. Induction of miRs-126/126* during both EB differentiation and colony formation reduced the number of erythroid colonies, suggesting an inhibitory role of miRs-126/126* in erythropoiesis. Protein tyrosine phosphatase, nonreceptor type 9 (PTPN9), a protein tyrosine phosphatase that is required for growth and expansion of erythroid cells, is one target of miR-126. PTPN9 restoration partially relieved the suppressed erythropoiesis caused by miRs-126/126*. Our results define an important function of miRs-126/126* in negative regulation of erythropoiesis, providing the first evidence for a role of miR in hematopoietic differentiation of hESCs.


2021 ◽  
pp. jclinpath-2020-206927
Author(s):  
Maryam Ahmed Al Barashdi ◽  
Ahlam Ali ◽  
Mary Frances McMullin ◽  
Ken Mills

The leucocyte common antigen, protein tyrosine phosphatase receptor type C (PTPRC), also known as CD45, is a transmembrane glycoprotein, expressed on almost all haematopoietic cells except for mature erythrocytes, and is an essential regulator of T and B cell antigen receptor-mediated activation. Disruption of the equilibrium between protein tyrosine kinase and phosphatase activity (from CD45 and others) can result in immunodeficiency, autoimmunity, or malignancy. CD45 is normally present on the cell surface, therefore it works upstream of a large signalling network which differs between cell types, and thus the effects of CD45 on these cells are also different. However, it is becoming clear that CD45 plays an essential role in the innate immune system and this is likely to be a key area for future research. In this review of PTPRC (CD45), its structure and biological activities as well as abnormal expression of CD45 in leukaemia and lymphoma will be discussed.


2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Chad M. Teven ◽  
Xing Liu ◽  
Ning Hu ◽  
Ni Tang ◽  
Stephanie H. Kim ◽  
...  

Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells. Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Owing to their ease of isolation and unique characteristics, MSCs have been widely regarded as potential candidates for tissue engineering and repair. While various signaling molecules important to MSC differentiation have been identified, our complete understanding of this process is lacking. Recent investigations focused on the role of epigenetic regulation in lineage-specific differentiation of MSCs have shown that unique patterns of DNA methylation and histone modifications play an important role in the induction of MSC differentiation toward specific lineages. Nevertheless, MSC epigenetic profiles reflect a more restricted differentiation potential as compared to ES cells. Here we review the effect of epigenetic modifications on MSC multipotency and differentiation, with a focus on osteogenic and adipogenic differentiation. We also highlight clinical applications of MSC epigenetics and nuclear reprogramming.


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