دانلود مقاله انتقال مکانیکی در سلول های بنیادی
خلاصه
1. معرفی
2. ریزمحیط سلول های بنیادی
3. مکانیسم‌های عمومی فرآیندهای حس‌کننده مکانیکی و مکانیکی با واسطه اینتگرین
4. مکانیزم زیست شناسی و فرآیندهای انتقال مکانی در سلول های بنیادی چند توان و پرتوان
5. انتقال مکانیکی هسته ای در سلول های (بنیادی).
6. نتیجه گیری
بیانیه مشارکت نویسنده CRediT
اعلامیه منافع رقابتی
سپاسگزاریها
در دسترس بودن داده ها
منابع
Abstract
1. Introduction
2. Stem cell microenvironment
3. General mechanisms of integrin-mediated mechanosensing and mechanotransductive processes
4. Mechanobiology and mechanotransductive processes in multi- and pluripotent stem cells
5. Nuclear mechanotransduction in (stem) cells
6. Conclusions
CRediT authorship contribution statement
Declaration of Competing Interest
Acknowledgements
Data availability
References
چکیده:
امروزه، این یک مفهوم ثابت شده است که توانایی دستیابی به یک هویت سلولی تخصصی از طریق تمایز، مانند سلول های بنیادی چند و چند توان، نه تنها توسط عوامل بیوشیمیایی تعیین می شود، بلکه جنبه های فیزیکی ریزمحیط نیز نقش کلیدی ایفا می کند. نقش؛ توسط سلول از طریق یک مسیر سیگنالینگ مبتنی بر نیرو به نام mechanotransduction تفسیر می شود. با این حال، پیوندهای پیچیده بین عناصر دخیل در انتقال مکانیکی، مانند ماتریکس خارج سلولی، گلیکوکالیکس، غشای سلولی، کمپلکس های چسبندگی اینتگرین، چسبندگی سلول/سلول با واسطه کادرین، اسکلت سلولی و هسته، هنوز از درک دور هستند. به تفصیل در اینجا آنچه را که در حال حاضر درباره این عناصر به طور کلی و اثر متقابل خاص آنها در زمینه سلول های بنیادی چند و چند توان شناخته شده است، گزارش می کنیم. علاوه بر این، ما این نمای کلی را با یک تصویر جامع تر ادغام می کنیم، که هدف آن پوشش کل مسیر مکانیکی انتقال دهنده از رابط سلول / میکرو محیط تا تنظیم ساختار کروماتین در هسته است. در نهایت، با این بررسی، تصویر فعلی از تعامل بین نشانه‌های مکانیکی انتقال و تنظیم اپی ژنتیک و اینکه چگونه این فرآیندها ممکن است به پویایی و سرنوشت سلول‌های بنیادی کمک کنند را ترسیم می‌کنیم.
Abstract
Nowadays, it is an established concept that the capability to reach a specialised cell identity via differentiation, as in the case of multi- and pluripotent stem cells, is not only determined by biochemical factors, but that also physical aspects of the microenvironment play a key role; interpreted by the cell through a force-based signalling pathway called mechanotransduction. However, the intricate ties between the elements involved in mechanotransduction, such as the extracellular matrix, the glycocalyx, the cell membrane, Integrin adhesion complexes, Cadherin-mediated cell/cell adhesion, the cytoskeleton, and the nucleus, are still far from being understood in detail. Here we report what is currently known about these elements in general and their specific interplay in the context of multi- and pluripotent stem cells. We furthermore merge this overview to a more comprehensive picture, that aims to cover the whole mechanotransductive pathway from the cell/microenvironment interface to the regulation of the chromatin structure in the nucleus. Ultimately, with this review we outline the current picture of the interplay between mechanotransductive cues and epigenetic regulation and how these processes might contribute to stem cell dynamics and fate.
Introduction
One of the basic principles enabling multicellular life is the differentiation of stem cells (SCs), into specialised cells with a defined identity, shape, and function ( McBeath et al., 2004 ) ( Tewary et al., 2018 ). SCs are defined as cells that are clonogenic, which defines their capability of both, self-renewing and retaining multilineage differentiation potency. In vertebrates, the Zygote represents the earliest stem cell (totipotent) in ontogeny, from which originate the pluripotent stem cells (PSCs) of the inner cell mass of the blastocyst ( Dean et al., 2003 , Smith, 2017 ). Soon thereafter, PSCs continue to expand during embryo development becoming progressively committed in their cell fate and acquiring a more restricted potency ( Dean et al., 2003 , Osorno et al., 2012 , Smith, 2017 ). Even at the end of embryogenesis, when the organism is fully formed, and its organs are composed of functionally mature cells, some SCs are still present. These cells, which possess a more limited differentiating potential (multipotent), in turn, give rise to a progeny of precursor cells and, finally, to functionally mature cells. Some examples are represented by the hematopoietic SCs in the bone marrow, the intestinal SCs in the gut’s crypts, the epithelial SCs in the epidermis or the mesenchymal stem cells (MSCs) which play an important role in the maintenance and regeneration of bones and cartilage ( Barker, 2014 , Evans et al., 2013 , Guan et al., 2012 , Tewary et al., 2018 , Watt, 2002 , Weissman, 2000 ).
The inherent high level of plasticity characterising SCs is at the base of their capability to respond precisely to appropriate stimuli with differentiative behaviour. Understanding this essential principle of multicellular life; i.e., the regulation of cell identity and fate, is one of the most important fields of research in modern cell biology, primarily due to its impact on the development of new therapeutic approaches in regenerative medicine. Such knowledge can directly benefit stem cell bioengineering by leveraging the SC plasticity and control over SC behaviour for the application in tissue engineering, patient-specific disease modelling and cell therapies ( Tewary et al., 2018 ).
Conclusions
In recent years there has been a fascinating expansion of our knowledge about the interplay between mechanotransductive signalling and chromatin regulation, and how this impacts on multi- and pluripotent stem cell dynamics, which we try to highlight in this review.
However, what shapes the life of a cell and its identity, from the outside (biophysical and structural cues of the cellular microenvironment) and from the inside (nuclear and chromatin organisation) and how it is connected (mechanotransduction and epigenetics) are highly relevant biological issues that are yet far from being understood in detail. Starting from the stem cell/microenvironment interface, a much more detailed understanding of the nanoscale events in this interface is necessary to unravel 1) what the SC perceives of the biophysical nature and the 3D adhesion site configuration and 2) how the immanent nanoscale information is interpreted and converted, through force-based actions, into a remodelling at the level of the IACs, cell/cell adhesions, cytoskeleton and nucleus.