scholarly journals Response to Stimulations Inducing Circadian Rhythm in Human Induced Pluripotent Stem Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 620
Author(s):  
Hitomi Kaneko ◽  
Taku Kaitsuka ◽  
Kazuhito Tomizawa

Regenerative medicine and disease modeling are expanding rapidly, through the development of human-induced pluripotent stem cells (hiPSCs). Many exogeneous supplements are often used for the directed differentiation of hiPSCs to specific lineages, such as chemicals and hormones. Some of these are known to synchronize the circadian clock, like forskolin (Frk) and dexamethasone (Dex); however, the response to these stimulations has not been fully elucidated for hiPSCs. In this study, we examined the response of clock genes to synchronizing stimulation, and compared it with fully differentiated cells, U2OS, and fibroblasts. The expression of clock genes did not show circadian rhythms in hiPSCs with Frk and Dex, which could be due to the significantly low levels of BMAL1. On the other hand, a circadian-like rhythm of D-box binding protein (DBP) expression was observed in hiPSCs by culturing them in an environment with a simulated body temperature. However, the inhibition of temperature-inducible factors, which are involved in temperature rhythm-induced synchronization, could not repress the expression of such rhythms, while the inhibition of HIF-1α significantly repressed them. In summary, we suggest that clock genes do not respond to the synchronizing agents in hiPSCs; instead, a unique circadian-like rhythm is induced by the temperature rhythm.

2021 ◽  
Author(s):  
Connie L Jiang ◽  
Yogesh Goyal ◽  
Naveen Jain ◽  
Qiaohong Wang ◽  
Rachel E Truitt ◽  
...  

Cardiac directed differentiation of human induced pluripotent stem cells consistently produces a mixed population of cardiomyocytes and non-cardiac cell types even when using very well-characterized protocols. We wondered whether differentiated cell types might result from intrinsic differences in hiPS cells prior to the onset of differentiation. By associating individual differentiated cells that share a common hiPS cell precursor, we were able to test whether expression variability in differentiated cells was pre-determined from the hiPS cell state. Although within a single experiment, differentiated cells that share an hiPS cell progenitor were more transcriptionally similar to each other than to other cells in the differentiated population, when the same hiPS cells were differentiated in parallel, we did not observe high transcriptional similarity across differentiations. Additionally, we found that substantial cell death occurred during differentiation in a manner that suggested that all cells were equally likely to survive or die, suggesting that there was no intrinsic selection bias for cells descended from particular hiPS cell progenitors. These results led us to wonder about how cells grow out spatially during the directed differentiation process. Labeling cells by their expression of a few canonical cell type marker genes, we showed that cells expressing the same marker tended to occur in patches observable by visual inspection, suggesting that cell type determination across multiple cell types, once initiated, is maintained in a cell-autonomous manner for multiple divisions. Altogether, our results show that while there is substantial heterogeneity in the initial hiPS cell population, that heterogeneity is not responsible for heterogeneous outcomes, and that the window during which cell type specification occurs is likely to begin shortly after the seeding of hiPS cells for differentiation.


2010 ◽  
Vol 34 (8) ◽  
pp. S36-S36
Author(s):  
Ping Duan ◽  
Xuelin Ren ◽  
Wenhai Yan ◽  
Xuefei Han ◽  
Xu Yan ◽  
...  

2016 ◽  
Vol 17 (2) ◽  
pp. 256 ◽  
Author(s):  
Mohammed Kawser Hossain ◽  
Ahmed Abdal Dayem ◽  
Jihae Han ◽  
Subbroto Kumar Saha ◽  
Gwang-Mo Yang ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Thekkeparambil Chandrabose Srijaya ◽  
Padmaja Jayaprasad Pradeep ◽  
Rosnah Binti Zain ◽  
Sabri Musa ◽  
Noor Hayaty Abu Kasim ◽  
...  

Induced pluripotent stem cell-based therapy for treating genetic disorders has become an interesting field of research in recent years. However, there is a paucity of information regarding the applicability of induced pluripotent stem cells in dental research. Recent advances in the use of induced pluripotent stem cells have the potential for developing disease-specific iPSC linesin vitrofrom patients. Indeed, this has provided a perfect cell source for disease modeling and a better understanding of genetic aberrations, pathogenicity, and drug screening. In this paper, we will summarize the recent progress of the disease-specific iPSC development for various human diseases and try to evaluate the possibility of application of iPS technology in dentistry, including its capacity for reprogramming some genetic orodental diseases. In addition to the easy availability and suitability of dental stem cells, the approach of generating patient-specific pluripotent stem cells will undoubtedly benefit patients suffering from orodental disorders.


2021 ◽  
Author(s):  
Dimitrios Voulgaris ◽  
Polyxeni Nikolakopoulou ◽  
Anna Herland

Generating astrocytes from induced pluripotent stem cells has been hampered by either prolonged differentiation -spanning over two months -or by shorter protocols that generate immature astrocytes, devoid of salient inflammation-associated astrocytic traits pivotal for CNS neuropathological modeling. We directed human neural stem cells derived from induced pluripotent stem cells to astrocytic commitment and maturity by orchestrating an astrocytic-tuned culturing environment. In under 28 days, the generated cells express canonical and mature astrocytic markers, denoted by the expression of AQP4 and, remarkably, the expression and functionality of glutamate transporter EAAT2. We also show that this protocol generates astrocytes that encompass traits critical in CNS disease modeling, such as glutathione synthesis and secretion, upregulation of ICAM-1 and a cytokine secretion profile which is on par with primary astrocytes. This protocol generates a multifaceted astrocytic model suitable for CNS in vitro disease modeling and personalized medicine through brain-on-chip technologies.


2018 ◽  
Vol 13 (7) ◽  
pp. 1662-1685 ◽  
Author(s):  
Samira Musah ◽  
Nikolaos Dimitrakakis ◽  
Diogo M. Camacho ◽  
George M. Church ◽  
Donald E. Ingber

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Guang-Yin Peng ◽  
Yang Lin ◽  
Jing-Jing Li ◽  
Ying Wang ◽  
Hao-Yue Huang ◽  
...  

Vascular disorders are complex diseases with high morbidity and mortality. Among them, the dilated macrovascular diseases (MVD), such as aortic aneurysm and aortic dissection, have presented a huge threat to human health. The pathogenesis of vascular diseases is mostly associated with property alteration of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). Studies have confirmed that induced pluripotent stem cells (iPSCs) can be proliferated and differentiated into other somatic cells, such as VECs and VSMCs. And patient-specific cells could provide detailed human-associated information in regard to pathogenesis or drug responses. In addition, differentiated ECs from iPSC have been widely used in disease modeling as a cell therapy. In this review, we mainly discussed the application of hiPSCs in investigating the pathological mechanism of different inherited vascular diseases and provide a comprehensive understanding of hiPSCs in the field of clinical diagnosis and gene therapy.


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