CDK11 safeguards the identity of human embryonic stem cells via fine‐tuning signaling pathways

2019 ◽  
Vol 235 (5) ◽  
pp. 4279-4290
Author(s):  
Jianyi Ding ◽  
Zhuoqing Fang ◽  
Xinyuan Liu ◽  
Zhexin Zhu ◽  
Chunsheng Wen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Signaling Pathways ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Fine Tuning

scholarly journals Expression profiles of protein tyrosine kinase genes in human embryonic stem cells

Reproduction ◽  
2008 ◽  
Vol 136 (4) ◽  
pp. 423-432 ◽  
Author(s):  
Mi-Young Son ◽  
Janghwan Kim ◽  
Hyo-Won Han ◽  
Sun-Mi Woo ◽  
Yee Sook Cho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Signaling Pathways ◽  
Human Embryonic Stem Cells ◽  
Tyrosine Kinases ◽  
Expression Profiles ◽  
Embryonic Stem ◽  
Degenerate Primers ◽  
Protein Tyrosine ◽  
Hesc Lines

Complex signaling pathways operate in human embryonic stem cells (hESCs) and are coordinated to maintain self-renewal and stem cell characteristics in them. Protein tyrosine kinases (PTKs) participate in diverse signaling pathways in various types of cells. Because of their functions as key molecules in various cellular processes, PTKs are anticipated to have important roles also in hESCs. In this study, we investigated the roles of PTKs in undifferentiated and differentiated hESCs. To establish comprehensive PTK expression profiles in hESCs, we performed reverse transcriptase PCR using degenerate primers according to the conserved catalytic PTK motifs in both undifferentiated and differentiated hESCs. Here, we identified 42 different kinases in two hESC lines, including 5 non-receptor tyrosine kinases (RTKs), 24 RTKs, and 13 dual and other kinases, and compared the protein kinase expression profiles of hESCs and retinoic acid-treated hESCs. Significantly, up- and downregulated kinases in undifferentiated hESCs were confirmed by real-time PCR and western blotting. MAP3K3, ERBB2, FGFR4, and EPHB2 were predominantly upregulated, while CSF1R, TYRO3, SRC, and GSK3A were consistently downregulated in two hESC lines. Western blot analysis showed that the transcriptional levels of these kinases were consistent with the translational levels. The obstruction of upregulated kinases’ activities using specific inhibitors disturbed the undifferentiated status and induced the differentiation of hESCs. Our results support the dynamic expression of PTKs during hESC maintenance and suggest that specific PTKs that are consistently up- and downregulated play important roles in the maintenance of stemness and the direction of differentiation of hESCs.

scholarly journals Fine Tuning of Hepatocyte Differentiation from Human Embryonic Stem Cells: Growth Factor vs. Small Molecule-Based Approaches

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Divya S. Varghese ◽  
Thilina Thejinda Alawathugoda ◽  
Suraiya A. Ansari
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Growth Factor ◽  
Small Molecule ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
The Body ◽  
Fine Tuning ◽  
Specific Marker ◽  
Hepatocyte Differentiation

Human embryonic stem cells (hESCs) are being utilized in diverse areas of studies such as development and disease modeling, cell replacement therapy, or drug toxicity testing because of their potential to be differentiated into any cell type in the body. The directed differentiation of hESCs into hepatocytes could provide an invaluable source of liver cells for various liver-based applications. Therefore, several protocols have been established in the past for hESC-hepatocyte differentiation based on the knowledge of signaling pathways and growth factors involved in different stages of embryonic hepatogenesis. Although successful derivation of hepatocytes has been achieved through these protocols, the efficiency is not always ideal. Herein, we have tested several combinations of published protocols, for example, growth factor vs. small molecule and different time durations of treatment for definitive endoderm (DE) induction and further hepatocyte differentiation to develop an efficient DE induction and hepatocyte differentiation in a highly reproducible manner based on the stage-specific marker expression and functional analysis.

scholarly journals Analysis of alternative signaling pathways of endoderm induction of human embryonic stem cells identifies context specific differences

2012 ◽  
Vol 6 (1) ◽  
pp. 154 ◽  
Author(s):  
Shibin Mathew ◽  
Maria Jaramillo ◽  
Xinan Zhang ◽  
Li Zhang ◽  
Alejandro Soto-Gutiérrez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Signaling Pathways ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Context Specific

scholarly journals In vitro modeling of hyperpigmentation associated to neurofibromatosis type 1 using melanocytes derived from human embryonic stem cells

2015 ◽  
Vol 112 (29) ◽  
pp. 9034-9039 ◽  
Author(s):  
Jennifer Allouche ◽  
Nathalia Bellon ◽  
Manoubia Saidani ◽  
Laure Stanchina-Chatrousse ◽  
Yolande Masson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Signaling Pathways ◽  
Human Embryonic Stem Cells ◽  
Neurofibromatosis Type 1 ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Neurofibromatosis Type

“Café-au-lait” macules (CALMs) and overall skin hyperpigmentation are early hallmarks of neurofibromatosis type 1 (NF1). One of the most frequent monogenic diseases, NF1 has subsequently been characterized with numerous benign Schwann cell-derived tumors. It is well established that neurofibromin, the NF1 gene product, is an antioncogene that down-regulates the RAS oncogene. In contrast, the molecular mechanisms associated with alteration of skin pigmentation have remained elusive. We have reassessed this issue by differentiating human embryonic stem cells into melanocytes. In the present study, we demonstrate that NF1 melanocytes reproduce the hyperpigmentation phenotype in vitro, and further characterize the link between loss of heterozygosity and the typical CALMs that appear over the general hyperpigmentation. Molecular mechanisms associated with these pathological phenotypes correlate with an increased activity of cAMP-mediated PKA and ERK1/2 signaling pathways, leading to overexpression of the transcription factor MITF and of the melanogenic enzymes tyrosinase and dopachrome tautomerase, all major players in melanogenesis. Finally, the hyperpigmentation phenotype can be rescued using specific inhibitors of these signaling pathways. These results open avenues for deciphering the pathological mechanisms involved in pigmentation diseases, and provide a robust assay for the development of new strategies for treating these diseases.

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