Protein Kinases and Associated Pathways in Pluripotent State and Lineage Differentiation

Shoni, Melina; Lui, Kathy O.; Vavvas, Demetrios G.; Muto, Michael G.; Berkowitz, Ross S.; Vlahos, Nikolaos; Ng, Sook Kien

doi:10.2174/1574888x09666140616130217

Cited by 9 publications

(8 citation statements)

References 329 publications

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“…Although the signaling pathways involved in dedifferentiation, transdifferentiation, and reprogramming have not been completely elucidated, recent evidence suggests that these pathways may have a critical role in application of stem cell therapy. 117 The Wnt/β-catenin, TGF-β, PI3K/Akt, Activin/Nodal, and Jak-Stat signaling pathways all have an essential role in pluripotency. 118 Recognizing which signaling pathways play a key role during dedifferentiation, transdifferentiation, and reprogramming could conceivably allow development of new approaches to control these processes through better control of the process of pluripotency.…”

Section: Discussionmentioning

confidence: 99%

Regulators of pluripotency and their implications in regenerative medicine

El-Badawy

El‐Badri

2015

SCCAA

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The ultimate goal of regenerative medicine is to replace damaged tissues with new functioning ones. This can potentially be accomplished by stem cell transplantation. While stem cell transplantation for blood diseases has been increasingly successful, widespread application of stem cell therapy in the clinic has shown limited results. Despite successful efforts to refine existing methodologies and to develop better ones for reprogramming, clinical application of stem cell therapy suffers from issues related to the safety of the transplanted cells, as well as the low efficiency of reprogramming technology. Better understanding of the underlying mechanism(s) involved in pluripotency should accelerate the clinical application of stem cell transplantation for regenerative purposes. This review outlines the main decision-making factors involved in pluripotency, focusing on the role of microRNAs, epigenetic modification, signaling pathways, and toll-like receptors. Of special interest is the role of toll-like receptors in pluripotency, where emerging data indicate that the innate immune system plays a vital role in reprogramming. Based on these data, we propose that nongenetic mechanisms for reprogramming provide a novel and perhaps an essential strategy to accelerate application of regenerative medicine in the clinic.

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Section: Discussionmentioning

confidence: 99%

Regulators of pluripotency and their implications in regenerative medicine

El-Badawy

El‐Badri

2015

SCCAA

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“…On the other hand, intricate signaling networks of protein kinases (PKs) are well known to be involved in regulating cellular events related to cell survival [67]. PK networks represent a significant mechanism by which cellular pluripotency and survival of hiPSCs are regulated [68][69][70]. To gain a more complete knowledge of cellular processes, we believe that additional phosphoproteome studies are needed to increase our comprehension of the different mechanisms and their fine-tuning involved in hiPSC response to hyperosmolarity stress.…”

Section: Discussionmentioning

confidence: 99%

Hyperosmotic Stress Induces a Specific Pattern for Stress Granule Formation in Human-Induced Pluripotent Stem Cells

Salloum-Asfar

Engelke

Mousa

et al. 2021

Stem Cells International

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Stress granules (SGs) are assemblies of selective messenger RNAs (mRNAs), translation factors, and RNA-binding proteins in small untranslated messenger ribonucleoprotein (mRNP) complexes in the cytoplasm. Evidence indicates that different types of cells have shown different mechanisms to respond to stress and the formation of SGs. In the present work, we investigated how human-induced pluripotent stem cells (hiPSCs/IMR90-1) overcome hyperosmotic stress compared to a cell line that does not harbor pluripotent characteristics (SH-SY5Y cell line). Gradient concentrations of NaCl showed a different pattern of SG formation between hiPSCs/IMR90-1 and the nonpluripotent cell line SH-SY5Y. Other pluripotent stem cell lines (hiPSCs/CRTD5 and hESCs/H9 (human embryonic stem cell line)) as well as nonpluripotent cell lines (BHK-21 and MCF-7) were used to confirm this phenomenon. Moreover, the formation of hyperosmotic SGs in hiPSCs/IMR90-1 was independent of eIF2α phosphorylation and was associated with low apoptosis levels. In addition, a comprehensive proteomics analysis was performed to identify proteins involved in regulating this specific pattern of hyperosmotic SG formation in hiPSCs/IMR90-1. We found possible implications of microtubule organization on the response to hyperosmotic stress in hiPSCs/IMR90-1. We have also unveiled a reduced expression of tubulin that may protect cells against hyperosmolarity stress while inhibiting SG formation without affecting stem cell self-renewal and pluripotency. Our observations may provide a possible cellular mechanism to better understand SG dynamics in pluripotent stem cells.

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“…The balance between the self-renewal and differentiation of PSCs is crucial for the developmental process and tissue homeostasis [87]. Specific regulatory protein kinases and their inhibitors have been shown to control the intracellular signaling network for the differentiation of PSCs towards a lineage-restricted state [88]. For example, inhibition of ROCK which is involved in various physiological cellular functions including migration, apoptosis, and proliferation [89] by Y-27632 or HA-100 improves the cloning efficiencies and single-cell survival of hPSCs [40, 90] but stimulates the differentiation of mPSCs into motor and sensory neurons [91] or the cardiac lineage [92].…”

Section: Kinase Inhibitors In Lineage Commitment and Differentiationmentioning

confidence: 99%

Protein Kinases and Their Inhibitors in Pluripotent Stem Cell Fate Regulation

Lee

Park

Jung

2019

Stem Cells International

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Protein kinases modulate the reversible postmodifications of substrate proteins to their phosphorylated forms as an essential process in regulating intracellular signaling transduction cascades. Moreover, phosphorylation has recently been shown to tightly control the regulatory network of kinases responsible for the induction and maintenance of pluripotency, defined as the particular ability to differentiate pluripotent stem cells (PSCs) into every cell type in the adult body. In particular, emerging evidence indicates that the balance between the self-renewal and differentiation of PSCs is regulated by the small molecules that modulate kinase signaling pathways. Furthermore, new reprogramming technologies have been developed using kinase modulators, which have provided novel insight of the mechanisms underlying the kinase regulatory networks involved in the generation of induced pluripotent stem cells (iPSCs). In this review, we highlight the recent progress made in defining the roles of protein kinase signaling pathways and their small molecule modulators in regulating the pluripotent states, self-renewal, reprogramming process, and lineage differentiation of PSCs.

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Protein Kinases and Associated Pathways in Pluripotent State and Lineage Differentiation

Cited by 9 publications

References 329 publications

Regulators of pluripotency and their implications in regenerative medicine

Regulators of pluripotency and their implications in regenerative medicine

Hyperosmotic Stress Induces a Specific Pattern for Stress Granule Formation in Human-Induced Pluripotent Stem Cells

Protein Kinases and Their Inhibitors in Pluripotent Stem Cell Fate Regulation

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