Chemical reprogramming for cell fate manipulation: Methods, applications, and perspectives

Wang, Jinlin; Sun, Shicheng; Deng, Hongkui

doi:10.1016/j.stem.2023.08.001

Cited by 26 publications

(6 citation statements)

References 157 publications

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“…One makes use of reprogramming TFs ( Takahashi and Yamanaka, 2006 ), while the other, which was developed more recently, uses a cocktail of several low-molecular-weight inhibitors and activators ( Hou et al, 2013 ). These approaches appear to be quite different in terms of the molecular mechanisms, staging, timing, and epigenetics of reprogramming, and a chemical-based approach has been practically uninvestigated in terms of its metabolic regulation [reviewed in ( Meir and Li, 2021 ; Lange et al, 2022 ; Wang et al, 2023 )]. Here, we discuss mainly the current view of the metabolic characteristics described for reprogramming from terminally differentiated somatic cells to pluripotent stem cells using the transgene-based strategy.…”

Section: Main Characteristics Of the Stages Of Reprogramming Toward P...mentioning

confidence: 99%

Metabolic control of induced pluripotency

Sinenko,

Tomilin

2024

Front. Cell Dev. Biol.

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Pluripotent stem cells of the mammalian epiblast and their cultured counterparts—embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs)—have the capacity to differentiate in all cell types of adult organisms. An artificial process of reactivation of the pluripotency program in terminally differentiated cells was established in 2006, which allowed for the generation of induced pluripotent stem cells (iPSCs). This iPSC technology has become an invaluable tool in investigating the molecular mechanisms of human diseases and therapeutic drug development, and it also holds tremendous promise for iPSC applications in regenerative medicine. Since the process of induced reprogramming of differentiated cells to a pluripotent state was discovered, many questions about the molecular mechanisms involved in this process have been clarified. Studies conducted over the past 2 decades have established that metabolic pathways and retrograde mitochondrial signals are involved in the regulation of various aspects of stem cell biology, including differentiation, pluripotency acquisition, and maintenance. During the reprogramming process, cells undergo major transformations, progressing through three distinct stages that are regulated by different signaling pathways, transcription factor networks, and inputs from metabolic pathways. Among the main metabolic features of this process, representing a switch from the dominance of oxidative phosphorylation to aerobic glycolysis and anabolic processes, are many critical stage-specific metabolic signals that control the path of differentiated cells toward a pluripotent state. In this review, we discuss the achievements in the current understanding of the molecular mechanisms of processes controlled by metabolic pathways, and vice versa, during the reprogramming process.

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Section: Main Characteristics Of the Stages Of Reprogramming Toward P...mentioning

confidence: 99%

Metabolic control of induced pluripotency

Sinenko,

Tomilin

2024

Front. Cell Dev. Biol.

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“…Chemical reprogramming offers a unique opportunity to control the fate of somatic cells and generate the desired cell types, including pluripotent stem cells for potential medical applications [ 11 ]. Human somatic cells chemically reprogrammed by activating a regeneration-like program may provide an alternative way of producing stem cells for clinical use.…”

Section: Stem Cell Medicine: Updated Research Highlightsmentioning

confidence: 99%

Optimizing health-span: advances in stem cell medicine and longevity research

Zhang,

Chen,

Huang

2023

Medical Review

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“…Among these small molecules, Y27632, classified as a rho-associated protein kinase(ROCK) inhibitor, has been reported to promote adhesion, extended passages, anti-apoptosis, pigmentation, and morphological characteristics of hiPSC-RPE [ 13 , 14 ]. Repsox, also known as 616452, functions as an inhibitor of the transforming growth factor-beta (TGF-β) receptor and is widely used in iPSC reprogramming and lineage reprogramming due to its ability to replace Sox2 and c-Myc by inhibiting TGF-β signaling pathways [ 15 , 16 ]. Both Y27632 and Repsox are integral components of small molecule cocktails utilized in the direct reprogramming of human astrocytes into early neuroectodermal cells [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox

Wang,

Yang,

Chen

et al. 2024

J Biol Eng

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Background Retinal pigment epithelium (RPE) cell therapy is a promising way to treat many retinal diseases. However, obtaining transplantable RPE cells is time-consuming and less effective. This study aimed to develop novel strategies for generating engineered RPE patches with physiological characteristics. Results Our findings revealed that RPE cells derived from human induced pluripotent stem cells (hiPSCs) successfully self-assembled into spheroids. The RPE spheroids treated with Y27632 and Repsox had increased expression of epithelial markers and RPE-specific genes, along with improved cell viability and barrier function. Transcriptome analysis indicated enhanced cell adhesion and extracellular matrix (ECM) organization in RPE spheroids. These RPE spheroids could be seeded and bioprinted on collagen vitrigel (CV) membranes to construct engineered RPE sheets. Circular RPE patches, obtained by trephining a specific section of the RPE sheet, exhibited abundant microvilli and pigment particles, as well as reduced proliferative capacity and enhanced maturation. Conclusions Our study suggests that the supplementation of small molecules and 3D spheroid culture, as well as the bioprinting technique, can be effective methods to promote RPE cultivation and construct engineered RPE sheets, which may support future clinical RPE cell therapy and the development of RPE models for research applications.

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Chemical reprogramming for cell fate manipulation: Methods, applications, and perspectives

Cited by 26 publications

References 157 publications

Metabolic control of induced pluripotency

Metabolic control of induced pluripotency

Optimizing health-span: advances in stem cell medicine and longevity research

Tissue engineering RPE sheet derived from hiPSC-RPE cell spheroids supplemented with Y-27632 and RepSox

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