scholarly journals Thyroid Hormone Effect on the Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-Like Cells

2021 ◽  
Vol 14 (6) ◽  
pp. 544
Author(s):  
Mariia S. Bogacheva ◽  
Margarita A. Bystriakova ◽  
Yan-Ru Lou

Human induced pluripotent stem cells (hiPSCs) hold great potential as an unlimited source for obtaining hepatocyte-like cells (HLCs) for drug research. However, current applications of HLCs have been severely limited by the inability to produce mature hepatocytes from hiPSCs in vitro. Thyroid hormones are one of the hormones that surge during the perinatal period when liver maturation takes place. Here we assessed the influence of thyroid hormone on hepatic progenitor differentiation to HLCs. We analyzed gene and protein expression of early and late hepatic markers and demonstrated the selective activity of thyroid hormone on different genes. Particularly, we demonstrated thyroid hormone-dependent inhibition of the fetal hepatic marker AFP. Our study sheds light on the role of thyroid hormone during liver differentiation and maturation.

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 353
Author(s):  
Hyunah Lee ◽  
Paulina Nowosiad ◽  
Lucia M. Dutan Polit ◽  
Jack Price ◽  
Deepak P. Srivastava ◽  
...  

Apolipoprotein E (APOE) is a multifunctional protein that plays significant roles in important cellular mechanisms in peripheral tissues and is as well expressed in the central nervous system, notably by adult neural stem cells (NSCs) in the hippocampus. Evidence from animal studies suggest that APOE is critical for adult NSC maintenance. However, whether APOE has the potential to play a similar role in human NSCs has not been directly investigated. To address this question, we conducted a focused study characterising APOE gene and protein expression in an in vitro model of neural differentiation utilising human induced pluripotent stem cells. We found that APOE gene expression was dramatically decreased as the cells became more differentiated, indicating that APOE expression levels reflect the degree of cellular differentiation during neural induction. Furthermore, qualitative analysis results of immunocytochemistry showed that intracellular localisation of APOE protein becomes more pronounced as neural differentiation progresses. Taken together, our findings suggest a potential role for APOE in human NSC maintenance and justify further investigations being carried out to understand whether changes in APOE levels can directly impact the neurogenic capacity of human stem cells.


F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 353
Author(s):  
Hyunah Lee ◽  
Paulina Nowosiad ◽  
Lucia M. Dutan Polit ◽  
Jack Price ◽  
Deepak P. Srivastava ◽  
...  

Apolipoprotein E (APOE) is a multifunctional protein that plays significant roles in important cellular mechanisms in peripheral tissues and is as well expressed in the central nervous system, notably by adult neural stem cells (NSCs) in the hippocampus. Evidence from animal studies suggest that APOE is critical for adult NSC maintenance. However, whether APOE has the potential to play a similar role in human NSCs has not been directly investigated. To address this question, we conducted a focused study characterising APOE gene and protein expression in an in vitro model of neural differentiation utilising human induced pluripotent stem cells. We found that APOE gene expression was dramatically decreased as the cells became more differentiated, indicating that APOE expression levels reflect the degree of cellular differentiation during neural induction. Furthermore, qualitative analysis results of immunocytochemistry showed that intracellular localisation of APOE protein becomes more pronounced as neural differentiation progresses. Taken together, our findings suggest a potential role for APOE in human NSC maintenance and justify further investigations being carried out to understand whether changes in APOE levels can directly impact the neurogenic capacity of human stem cells.


2021 ◽  
Vol 22 (9) ◽  
pp. 4334
Author(s):  
Katrina Albert ◽  
Jonna Niskanen ◽  
Sara Kälvälä ◽  
Šárka Lehtonen

Induced pluripotent stem cells (iPSCs) are a self-renewable pool of cells derived from an organism’s somatic cells. These can then be programmed to other cell types, including neurons. Use of iPSCs in research has been two-fold as they have been used for human disease modelling as well as for the possibility to generate new therapies. Particularly in complex human diseases, such as neurodegenerative diseases, iPSCs can give advantages over traditional animal models in that they more accurately represent the human genome. Additionally, patient-derived cells can be modified using gene editing technology and further transplanted to the brain. Glial cells have recently become important avenues of research in the field of neurodegenerative diseases, for example, in Alzheimer’s disease and Parkinson’s disease. This review focuses on using glial cells (astrocytes, microglia, and oligodendrocytes) derived from human iPSCs in order to give a better understanding of how these cells contribute to neurodegenerative disease pathology. Using glia iPSCs in in vitro cell culture, cerebral organoids, and intracranial transplantation may give us future insight into both more accurate models and disease-modifying therapies.


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