Dynamic Mechanical Properties Control Adult Stem Cell Fate

2012 ◽  
Author(s):  
Murat Guvendiren ◽  
Jason A. Burdick
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Adult Stem Cell ◽  
Dynamic Mechanical Properties ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Proliferation And Differentiation ◽  
Important Field ◽  
Control Adult

Stem cells respond to many microenvironmental cues towards their decisions to spread, migrate, and differentiate and these cues can be incorporated into materials for regenerative medicine.1 In the last decade, matrix stiffness alone has been implicated in regulating cellular functions such as migration, proliferation and differentiation. With this in mind, a variety of natural and synthetic polymer systems were used in vitro to mimic the elasticity of native tissues. Despite helping to develop this important field and gather valuable information, these substrates are primarily static and lack the dynamic nature that is observed during many cellular processes such as development, fibrosis and cancer. Thus, it is of great interest to temporally manipulate matrix elasticity in vitro to better understand and develop strategies to control these biological processes. In this work, we utilize a sequential crosslinking approach (initial gelation via addition reaction, secondary crosslinking through light-mediated radical polymerization) to fabricate hydrogel substrates that stiffen (e.g., ∼3 to 30 kPa) either immediately or at later times and in the presence of cells. We demonstrate the utility of this technique by investigating the short-term (several minutes to hours) and long-term (several days to weeks) stem cell response to dynamic stiffening

scholarly journals Drosophila YBX1 homolog YPS promotes ovarian germ line stem cell development by preferentially recognizing 5-methylcytosine RNAs

2020 ◽  
Vol 117 (7) ◽  
pp. 3603-3609 ◽  
Author(s):  
Fan Zou ◽  
Renjun Tu ◽  
Bo Duan ◽  
Zhenlin Yang ◽  
Zhaohua Ping ◽  
...  
Keyword(s):  
Stem Cell ◽  
Rna Binding ◽  
Germ Line ◽  
Adult Stem Cell ◽  
Cell Development ◽  
Rna Modification ◽  
Proliferation And Differentiation ◽  
Germ Line Stem Cell ◽  
Rna Complex

5-Methylcytosine (m5C) is a RNA modification that exists in tRNAs and rRNAs and was recently found in mRNAs. Although it has been suggested to regulate diverse biological functions, whether m5C RNA modification influences adult stem cell development remains undetermined. In this study, we show that Ypsilon schachtel (YPS), a homolog of human Y box binding protein 1 (YBX1), promotes germ line stem cell (GSC) maintenance, proliferation, and differentiation in the Drosophila ovary by preferentially binding to m5C-containing RNAs. YPS is genetically demonstrated to function intrinsically for GSC maintenance, proliferation, and progeny differentiation in the Drosophila ovary, and human YBX1 can functionally replace YPS to support normal GSC development. Highly conserved cold-shock domains (CSDs) of YPS and YBX1 preferentially bind to m5C RNA in vitro. Moreover, YPS also preferentially binds to m5C-containing RNAs, including mRNAs, in germ cells. The crystal structure of the YBX1 CSD-RNA complex reveals that both hydrophobic stacking and hydrogen bonds are critical for m5C binding. Overexpression of RNA-binding–defective YPS and YBX1 proteins disrupts GSC development. Taken together, our findings show that m5C RNA modification plays an important role in adult stem cell development.

scholarly journals Controlling Redox Status for Stem Cell Survival, Expansion, and Differentiation

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Sébastien Sart ◽  
Liqing Song ◽  
Yan Li
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Disease Modeling ◽  
Redox Status ◽  
Culture Conditions ◽  
Ros Generation ◽  
Cellular Functions ◽  
Proliferation And Differentiation ◽  
Cell Organization

Reactive oxygen species (ROS) have long been considered as pathological agents inducing apoptosis under adverse culture conditions. However, recent findings have challenged this dogma and physiological levels of ROS are now considered as secondary messengers, mediating numerous cellular functions in stem cells. Stem cells represent important tools for tissue engineering, drug screening, and disease modeling. However, the safe use of stem cells for clinical applications still requires culture improvements to obtain functional cells. With the examples of mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs), this review investigates the roles of ROS in the maintenance of self-renewal, proliferation, and differentiation of stem cells. In addition, this work highlights that the tight control of stem cell microenvironment, including cell organization, and metabolic and mechanical environments, may be an effective approach to regulate endogenous ROS generation. Taken together, this paper indicates the need for better quantification of ROS towards the accurate control of stem cell fate.

Control of Adult Stem Cell Function in Bioengineered in vitro Niches

2008 ◽  
Author(s):  
Helen M. Blau ◽  
Matthias P. Lutolf
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Adult Stem Cell

scholarly journals Influence of a macroporous β-TCP structure on human mesenchymal stem cell proliferation and differentiation in vitro

Open Ceramics ◽  
2021 ◽  
pp. 100141
Author(s):  
Shaan Chamary ◽  
Liliana Grenho ◽  
Maria Helena Fernandes ◽  
Franck Bouchart ◽  
Fernando Jorge Monteiro ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Human Mesenchymal Stem Cell ◽  
Stem Cell Proliferation ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation

scholarly journals AUTOLOGOUS CORNEAL REPAIR USING IN-VITRO ADULT STEM CELL EXPANSION

2016 ◽  
Vol 2 (1) ◽  
pp. 1-7
Author(s):  
Charles McGhee ◽  
◽  
Peter J Wilson ◽  
Jeremy J Mathan ◽  
Jennifer J McGhee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Expansion ◽  
Adult Stem Cell ◽  
Stem Cell Expansion

scholarly journals A Human DUB Protein Array for Clarification of Linkage Specificity of Polyubiquitin Chain and Application to Evaluation of Its Inhibitors

Biomedicines ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 152
Author(s):  
Hirotaka Takahashi ◽  
Satoshi Yamanaka ◽  
Shohei Kuwada ◽  
Kana Higaki ◽  
Kohki Kido ◽  
...  
Keyword(s):  
Drug Targets ◽  
Protein Array ◽  
Polyubiquitin Chain ◽  
Deubiquitinating Enzymes ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Model Study ◽  
Biochemical Analyses ◽  
Almost All

Protein ubiquitinations play pivotal roles in many cellular processes, including homeostasis, responses to various stimulations, and progression of diseases. Deubiquitinating enzymes (DUBs) remove ubiquitin molecules from ubiquitinated proteins and cleave the polyubiquitin chain, thus negatively regulating numerous ubiquitin-dependent processes. Dysfunctions of many DUBs reportedly cause various diseases; therefore, DUBs are considered as important drug targets, although the biochemical characteristics and cellular functions of many DUBs are still unclear. Here, we established a human DUB protein array to detect the activity and linkage specificity of almost all human DUBs. Using a wheat cell-free protein synthesis system, 88 full-length recombinant human DUB proteins were prepared and termed the DUB array. In vitro DUB assays were performed with all of these recombinant DUBs, using eight linkage types of diubiquitins as substrates. As a result, 80 DUBs in the array showed DUB activities, and their linkage specificities were determined. These 80 DUBs included many biochemically uncharacterized DUBs in the past. In addition, taking advantage of these active DUB proteins, we applied the DUB array to evaluate the selectivities of DUB inhibitors. We successfully developed a high-throughput and semi-quantitative DUB assay based on AlphaScreen technology, and a model study using two commercially available DUB inhibitors revealed individual selectivities to 29 DUBs, as previously reported. In conclusion, the DUB array established here is a powerful tool for biochemical analyses and drug discovery for human DUBs.

scholarly journals N6-Methyladenosine in RNA and DNA: An Epitranscriptomic and Epigenetic Player Implicated in Determination of Stem Cell Fate

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Pengfei Ji ◽  
Xia Wang ◽  
Nina Xie ◽  
Yujing Li
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Direct Interaction ◽  
Limited Information ◽  
Stem Cell Fate ◽  
Base Modification ◽  
Dna And Rna ◽  
Proliferation And Differentiation

Vast emerging evidences are linking the base modifications and determination of stem cell fate such as proliferation and differentiation. Among the base modification markers extensively studied, 5-methylcytosine (5-mC) and its oxidative derivatives (5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC)) dynamically occur in DNA and RNA and have been acknowledged as important epigenetic markers involved in regulation of cellular biological processes. N6-Methyladenosine modification in DNA (m6dA), mRNA (m6A), tRNA, and other noncoding RNAs has been defined as another important epigenetic and epitranscriptomic marker in eukaryotes in recent years. The mRNA m6A modification has been characterized biochemically, molecularly, and phenotypically, including elucidation of its methyltransferase complexes (m6A writer), demethylases (m6A eraser), and direct interaction proteins (readers), while limited information on the DNA m6dA is available. The levels and the landscapes of m6A in the epitranscriptomes and epigenomes are precisely and dynamically regulated by the fine-tuned coordination of the writers and erasers in accordance with stages of the growth, development, and reproduction as naturally programmed during the lifespan. Additionally, progress has been made in appreciation of the link between aberrant m6A modification in stem cells and diseases, like cancers and neurodegenerative disorders. These achievements are inspiring scientists to further uncover the epigenetic mechanisms for stem cell development and to dissect pathogenesis of the multiple diseases conferred by development aberration of the stem cells. This review article will highlight the research advances in the role of m6A methylation modifications of DNA and RNA in the regulation of stem cell and genesis of the closely related disorders. Additionally, this article will also address the research directions in the future.

scholarly journals Regulation and Directing Stem Cell Fate by Tissue Engineering Functional Microenvironments: Scaffold Physical and Chemical Cues

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Fei Xing ◽  
Lang Li ◽  
Changchun Zhou ◽  
Cheng Long ◽  
Lina Wu ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Stem Cell ◽  
Growth Factors ◽  
Cell Fate ◽  
Chemical Cues ◽  
Physical Factors ◽  
Stem Cell Fate ◽  
Physical And Chemical

It is well known that stem cells reside within tissue engineering functional microenvironments that physically localize them and direct their stem cell fate. Recent efforts in the development of more complex and engineered scaffold technologies, together with new understanding of stem cell behavior in vitro, have provided a new impetus to study regulation and directing stem cell fate. A variety of tissue engineering technologies have been developed to regulate the fate of stem cells. Traditional methods to change the fate of stem cells are adding growth factors or some signaling pathways. In recent years, many studies have revealed that the geometrical microenvironment played an essential role in regulating the fate of stem cells, and the physical factors of scaffolds including mechanical properties, pore sizes, porosity, surface stiffness, three-dimensional structures, and mechanical stimulation may affect the fate of stem cells. Chemical factors such as cell-adhesive ligands and exogenous growth factors would also regulate the fate of stem cells. Understanding how these physical and chemical cues affect the fate of stem cells is essential for building more complex and controlled scaffolds for directing stem cell fate.

scholarly journals Oleanolic acid enhances neural stem cell migration, proliferation, and differentiation in vitro by inhibiting GSK3β activity

2018 ◽  
Vol 4 (1) ◽  
Author(s):  
Shi Qing Zhang ◽  
Kai Li Lin ◽  
Cheuk Yu Law ◽  
Bin Liu ◽  
Xiu Qiong Fu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Migration ◽  
Neural Stem Cell ◽  
Oleanolic Acid ◽  
Stem Cell Migration ◽  
Proliferation And Differentiation

scholarly journals Do not keep it simple: recent advances in the generation of complex organoids

2020 ◽  
Vol 127 (11) ◽  
pp. 1569-1577 ◽  
Author(s):  
Philipp Wörsdörfer ◽  
Takashi I ◽  
Izumi Asahina ◽  
Yoshinori Sumita ◽  
Süleyman Ergün
Keyword(s):  
Stem Cell ◽  
3D Cell Culture ◽  
Adult Stem Cell ◽  
Inflammatory Cells ◽  
Stem Cell Population ◽  
Special Focus ◽  
Differentiation Protocol ◽  
Organ Specific ◽  
Culture Models

Abstract 3D cell culture models which closely resemble real human tissues are of high interest for disease modelling, drug screening as well as a deeper understanding of human developmental biology. Such structures are termed organoids. Within the last years, several human organoid models were described. These are usually stem cell derived, arise by self-organization, mimic mechanisms of normal tissue development, show typical organ morphogenesis and recapitulate at least some organ specific functions. Many tissues have been reproduced in vitro such as gut, liver, lung, kidney and brain. The resulting entities can be either derived from an adult stem cell population, or generated from pluripotent stem cells using a specific differentiation protocol. However, many organoid models only recapitulate the organs parenchyma but are devoid of stromal components such as blood vessels, connective tissue and inflammatory cells. Recent studies show that the incorporation of endothelial and mesenchymal cells into organoids improved their maturation and might be required to create fully functional micro-tissues, which will allow deeper insights into human embryogenesis as well as disease development and progression. In this review article, we will summarize and discuss recent works trying to incorporate stromal components into organoids, with a special focus on neural organoid models.

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