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Small molecules for cell reprogramming: a systems biology analysis

If somatic stem cells would be able to maintain their regenerative capacity over time, this might, to a great extent, resolve rejuvenation issues. Unfortunately, the pool of somatic stem cells is limited, and they undergo cell aging with a consequent loss of functionality. During the last decade, lo...

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Autores principales: Knyazer, Anna, Bunu, Gabriela, Toren, Dmitri, Mracica, Teodora Bucaciuc, Segev, Yael, Wolfson, Marina, Muradian, Khachik K., Tacutu, Robi, Fraifeld, Vadim E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751603/
https://www.ncbi.nlm.nih.gov/pubmed/34919532
http://dx.doi.org/10.18632/aging.203791
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author Knyazer, Anna
Bunu, Gabriela
Toren, Dmitri
Mracica, Teodora Bucaciuc
Segev, Yael
Wolfson, Marina
Muradian, Khachik K.
Tacutu, Robi
Fraifeld, Vadim E.
author_facet Knyazer, Anna
Bunu, Gabriela
Toren, Dmitri
Mracica, Teodora Bucaciuc
Segev, Yael
Wolfson, Marina
Muradian, Khachik K.
Tacutu, Robi
Fraifeld, Vadim E.
author_sort Knyazer, Anna
collection PubMed
description If somatic stem cells would be able to maintain their regenerative capacity over time, this might, to a great extent, resolve rejuvenation issues. Unfortunately, the pool of somatic stem cells is limited, and they undergo cell aging with a consequent loss of functionality. During the last decade, low molecular weight compounds that are able to induce or enhance cell reprogramming have been reported. They were named “Small Molecules” (SMs) and might present definite advantages compared to the exogenous introduction of stemness-related transcription factors (e.g. Yamanaka’s factors). Here, we undertook a systemic analysis of SMs and their potential gene targets. Data mining and curation lead to the identification of 92 SMs. The SM targets fall into three major functional categories: epigenetics, cell signaling, and metabolic “switchers”. All these categories appear to be required in each SM cocktail to induce cell reprogramming. Remarkably, many enriched pathways of SM targets are related to aging, longevity, and age-related diseases, thus connecting them with cell reprogramming. The network analysis indicates that SM targets are highly interconnected and form protein-protein networks of a scale-free topology. The extremely high contribution of hubs to network connectivity suggests that (i) cell reprogramming may require SM targets to act cooperatively, and (ii) their network organization might ensure robustness by resistance to random failures. All in all, further investigation of SMs and their relationship with longevity regulators will be helpful for developing optimal SM cocktails for cell reprogramming with a perspective for rejuvenation and life span extension.
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spelling pubmed-87516032022-01-12 Small molecules for cell reprogramming: a systems biology analysis Knyazer, Anna Bunu, Gabriela Toren, Dmitri Mracica, Teodora Bucaciuc Segev, Yael Wolfson, Marina Muradian, Khachik K. Tacutu, Robi Fraifeld, Vadim E. Aging (Albany NY) Research Paper If somatic stem cells would be able to maintain their regenerative capacity over time, this might, to a great extent, resolve rejuvenation issues. Unfortunately, the pool of somatic stem cells is limited, and they undergo cell aging with a consequent loss of functionality. During the last decade, low molecular weight compounds that are able to induce or enhance cell reprogramming have been reported. They were named “Small Molecules” (SMs) and might present definite advantages compared to the exogenous introduction of stemness-related transcription factors (e.g. Yamanaka’s factors). Here, we undertook a systemic analysis of SMs and their potential gene targets. Data mining and curation lead to the identification of 92 SMs. The SM targets fall into three major functional categories: epigenetics, cell signaling, and metabolic “switchers”. All these categories appear to be required in each SM cocktail to induce cell reprogramming. Remarkably, many enriched pathways of SM targets are related to aging, longevity, and age-related diseases, thus connecting them with cell reprogramming. The network analysis indicates that SM targets are highly interconnected and form protein-protein networks of a scale-free topology. The extremely high contribution of hubs to network connectivity suggests that (i) cell reprogramming may require SM targets to act cooperatively, and (ii) their network organization might ensure robustness by resistance to random failures. All in all, further investigation of SMs and their relationship with longevity regulators will be helpful for developing optimal SM cocktails for cell reprogramming with a perspective for rejuvenation and life span extension. Impact Journals 2021-12-17 /pmc/articles/PMC8751603/ /pubmed/34919532 http://dx.doi.org/10.18632/aging.203791 Text en Copyright: © 2021 Knyazer et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Knyazer, Anna
Bunu, Gabriela
Toren, Dmitri
Mracica, Teodora Bucaciuc
Segev, Yael
Wolfson, Marina
Muradian, Khachik K.
Tacutu, Robi
Fraifeld, Vadim E.
Small molecules for cell reprogramming: a systems biology analysis
title Small molecules for cell reprogramming: a systems biology analysis
title_full Small molecules for cell reprogramming: a systems biology analysis
title_fullStr Small molecules for cell reprogramming: a systems biology analysis
title_full_unstemmed Small molecules for cell reprogramming: a systems biology analysis
title_short Small molecules for cell reprogramming: a systems biology analysis
title_sort small molecules for cell reprogramming: a systems biology analysis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751603/
https://www.ncbi.nlm.nih.gov/pubmed/34919532
http://dx.doi.org/10.18632/aging.203791
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