The Role of iPSC Modeling Toward Projection of Autophagy Pathway in Disease Pathogenesis: Leader or Follower

Kolahdouzmohammadi, Mina; Totonchi, Mehdi; Pahlavan, Sara

doi:10.1007/s12015-020-10077-8

Cited by 5 publications

(3 citation statements)

References 167 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conventional 2D human-derived induced neuronal stem cell models are derived from either human embryonal stem cells (ESC) ( Figure 1A ) or human-derived induced pluripotent stem cells (iPSC) ( Figure 1B ). These models have been used in growing numbers for studying autophagy in several late-onset neurodegenerative diseases and revealed autophagic alterations in connection with neurodegeneration ( Prajumwongs et al, 2016 ; Jungverdorben et al, 2017 ; Mertens et al, 2018 ; Kolahdouzmohammadi et al, 2021 ). ESC-derived neuronal models ( Figure 1A ) used to study cellular pathogenesis are present almost exclusively in stem cell transplantation experiments for ethical reasons ( Singh et al, 2016 ).…”

Section: Cellular Reprogramming Models To Study Autophagymentioning

confidence: 99%

Fountain of youth—Targeting autophagy in aging

Danics

Abbas

Kis

et al. 2023

Front. Aging Neurosci.

View full text Add to dashboard Cite

As our society ages inexorably, geroscience and research focusing on healthy aging is becoming increasingly urgent. Macroautophagy (referred to as autophagy), a highly conserved process of cellular clearance and rejuvenation has attracted much attention due to its universal role in organismal life and death. Growing evidence points to autophagy process as being one of the key players in the determination of lifespan and health. Autophagy inducing interventions show significant improvement in organismal lifespan demonstrated in several experimental models. In line with this, preclinical models of age-related neurodegenerative diseases demonstrate pathology modulating effect of autophagy induction, implicating its potential to treat such disorders. In humans this specific process seems to be more complex. Recent clinical trials of drugs targeting autophagy point out some beneficial effects for clinical use, although with limited effectiveness, while others fail to show any significant improvement. We propose that using more human-relevant preclinical models for testing drug efficacy would significantly improve clinical trial outcomes. Lastly, the review discusses the available cellular reprogramming techniques used to model neuronal autophagy and neurodegeneration while exploring the existing evidence of autophagy’s role in aging and pathogenesis in human-derived in vitro models such as embryonic stem cells (ESCs), induced pluripotent stem cell derived neurons (iPSC-neurons) or induced neurons (iNs).

show abstract

Section: Cellular Reprogramming Models To Study Autophagymentioning

confidence: 99%

Fountain of youth—Targeting autophagy in aging

Danics

Abbas

Kis

et al. 2023

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…It is one of the major intracellular degradation pathways through which cellular components are delivered to and degraded in the lysosome (Levine and Klionsky 2004). This biological process also contributes to cellular homeostasis, meaning that autophagy is not only limited to the elimination of cell cargo waste but also serves as a dynamic recycling system to provide energy (Deretic and Levine 2009; Kolahdouzmohammadi et al 2021). The main regulators of this biological pathway include the 5′ AMP‐activated protein kinase (AMPK) and, the mammalian target of rapamycin (mTOR) which activates and inhibits autophagy, respectively (Ho et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Activation of AMPK promotes cardiac differentiation by stimulating the autophagy pathway

Kolahdouzmohammadi

Pahlavan

Sotoodehnejadnematalahi

et al. 2023

J. Cell Commun. Signal.

Self Cite

View full text Add to dashboard Cite

Autophagy, a critical catabolic process for cell survival against different types of stress, has a role in the differentiation of various cells, such as cardiomyocytes. Adenosine 5ʹ‐monophosphate (AMP)‐activated protein kinase (AMPK) is an energy‐sensing protein kinase involved in the regulation of autophagy. In addition to its direct role in regulating autophagy, AMPK can also influence other cellular processes by regulating mitochondrial function, posttranslational acetylation, cardiomyocyte metabolism, mitochondrial autophagy, endoplasmic reticulum stress, and apoptosis. As AMPK is involved in the control of various cellular processes, it can influence the health and survival of cardiomyocytes. This study investigated the effects of an AMPK inducer (Metformin) and an autophagy inhibitor (Hydroxychloroquine) on the differentiation of human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CMs). The results showed that autophagy was upregulated during cardiac differentiation. Furthermore, AMPK activation increased the expression of CM‐specific markers in hPSC‐CMs. Additionally, autophagy inhibition impaired cardiomyocyte differentiation by targeting autophagosome‐lysosome fusion. These results indicate the significance of autophagy in cardiomyocyte differentiation. In conclusion, AMPK might be a promising target for the regulation of cardiomyocyte generation by in vitro differentiation of pluripotent stem cells.

show abstract

“…The involvement of autophagy has also been extensively studied and demonstrated in cardiomyocyte differentiation [9][10][11][12]. Autophagy, triggered by energy or nutrient deprivation or as a quality-control mechanism, is crucial for cellular homeostasis and survival by providing cells with building blocks and energy for cellular reconstruction and maintenance.…”

Section: Introductionmentioning

confidence: 99%

Revisiting the Role of Autophagy in Cardiac Differentiation: A Comprehensive Review of Interplay with Other Signaling Pathways

Kolahdouzmohammadi

Kolahdouz‐Mohammadi

Tabatabaei

et al. 2023

Genes

Self Cite

View full text Add to dashboard Cite

Autophagy is a critical biological process in which cytoplasmic components are sequestered in autophagosomes and degraded in lysosomes. This highly conserved pathway controls intracellular recycling and is required for cellular homeostasis, as well as the correct functioning of a variety of cellular differentiation programs, including cardiomyocyte differentiation. By decreasing oxidative stress and promoting energy balance, autophagy is triggered during differentiation to carry out essential cellular remodeling, such as protein turnover and lysosomal degradation of organelles. When it comes to controlling cardiac differentiation, the crosstalk between autophagy and other signaling networks such as fibroblast growth factor (FGF), Wnt, Notch, and bone morphogenetic proteins (BMPs) is essential, yet the interaction between autophagy and epigenetic controls remains poorly understood. Numerous studies have shown that modulating autophagy and precisely regulating it can improve cardiac differentiation, which can serve as a viable strategy for generating mature cardiac cells. These findings suggest that autophagy should be studied further during cardiac differentiation. The purpose of this review article is not only to discuss the relationship between autophagy and other signaling pathways that are active during the differentiation of cardiomyocytes but also to highlight the importance of manipulating autophagy to produce fully mature cardiomyocytes, which is a tough challenge.

show abstract

The Role of iPSC Modeling Toward Projection of Autophagy Pathway in Disease Pathogenesis: Leader or Follower

Cited by 5 publications

References 167 publications

Fountain of youth—Targeting autophagy in aging

Fountain of youth—Targeting autophagy in aging

Activation of AMPK promotes cardiac differentiation by stimulating the autophagy pathway

Revisiting the Role of Autophagy in Cardiac Differentiation: A Comprehensive Review of Interplay with Other Signaling Pathways

Contact Info

Product

Resources

About