Stem Cell Differentiation is Regulated by Extracellular Matrix Mechanics

Smith, Lucas; Cho, Sang-Kyun; Discher, Dennis E.

doi:10.1152/physiol.00026.2017

Cited by 210 publications

(164 citation statements)

References 100 publications

(99 reference statements)

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“…It is important to clarify that the analysis of single cells falls behind its importance if not associated with spatial information. Moreover, cells have their own identity because of the consistence (rigidity) of their ambient (extracellular matrix) [221][222][223]. The human body, for example, is formed by~100 trillion cells each spatially located in specific tissues with different softness where exerting their functions in a collaborative network with other cells.…”

Section: Discussionmentioning

confidence: 99%

A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs

Alessio

Bonadio

Buson

et al. 2020

IJMS

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In late 2012 it was evidenced that most of the human genome is transcribed but only a small percentage of the transcripts are translated. This observation supported the importance of non-coding RNAs and it was confirmed in several organisms. The most abundant non-translated transcripts are long non-coding RNAs (lncRNAs). In contrast to protein-coding RNAs, they show a more cell-specific expression. To understand the function of lncRNAs, it is fundamental to investigate in which cells they are preferentially expressed and to detect their subcellular localization. Recent improvements of techniques that localize single RNA molecules in tissues like single-cell RNA sequencing and fluorescence amplification methods have given a considerable boost in the knowledge of the lncRNA functions. In recent years, single-cell transcription variability was associated with non-coding RNA expression, revealing this class of RNAs as important transcripts in the cell lineage specification. The purpose of this review is to collect updated information about lncRNA classification and new findings on their function derived from single-cell analysis. We also retained useful for all researchers to describe the methods available for single-cell analysis and the databases collecting single-cell and lncRNA data. Tables are included to schematize, describe, and compare exposed concepts.Int. J. Mol. Sci. 2020, 21, 302 2 of 32 not achieved by transcription factors (TFs) alone because of their low number (approximately 1500 in mammals [4]) compared to genes to regulate (90% of the genome is transcribed in human [5]). A single TF is estimated to regulate only ten thousand genes according to Chromatin immunoprecipitation and DNA sequencing experiments (ChIp-seq) [6]. Moreover, the involvement of non-coding RNAs in gene expression regulation was evident [7,8]. The evidence that the non-protein coding component of the human genome is actively transcribed and carries out crucial functions limits the importance of coding genes in genome regulation. Non-coding transcripts become one of the stars of modern biology, especially because of their involvement in a wide range of regulatory processes and changed the association of non-coding regions to junk DNA [3].The genome of multicellular eukaryotes is mostly comprised of non-coding DNA (less than 2% of the human genome codes for proteins [9] while 90% of the human genome is transcribed). Non-coding DNA is transcribed into different classes of non-coding RNAs (ncRNAs) that include structural RNAs (rRNAs and tRNAs) and regulatory RNAs [10]. rRNAs and tRNAs are involved in mRNA translation and can be long or short in size. Regulatory RNAs are further divided into three classes: Small, medium, and long non-coding RNAs. Small non-coding RNAs are between 20 and 50 nucleotides long and include microRNAs (miRNAs) that participate in post-transcriptional regulation [11], small interfering RNAs (siRNAs) that are double-stranded RNAs involved in gene silencing through RNA interfering pathway [12], piwi interacting R...

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Section: Discussionmentioning

confidence: 99%

A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs

Alessio

Bonadio

Buson

et al. 2020

IJMS

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“…This can often limit the available materials processed for 3D printing, which hinders advances where additional material properties are needed for functionality of the printed constructs. Further, it is now well known that cells respond to a plethora of signals in their microenvironments from material mechanics to material degradability; thus, it is desirable to decouple the printing process from printability to further expand the materials that can be used in precision medicine approaches . Fortunately, numerous approaches have been developed that overcome these limitations, such as through material additives, sacrificial polymers, and in a re‐evaluation of how materials are deposited during the printing process ( Figure ).…”

Section: Advanced 3d Printing Technologiesmentioning

confidence: 99%

Recent Advances in Enabling Technologies in 3D Printing for Precision Medicine

2019

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Advances in areas such as data analytics, genomics, and imaging have revealed individual patient complexities and exposed the inherent limitations of generic therapies for patient treatment. These observations have also fueled the development of precision medicine approaches, where therapies are tailored for the individual rather than the broad patient population. 3D printing is a field that intersects with precision medicine through the design of precision implants with patient‐directed shapes, structures, and materials or for the development of patient‐specific in vitro models that can be used for screening precision therapeutics. Toward their success, advances in 3D printing and biofabrication technologies are needed with enhanced resolution, complexity, reproducibility, and speed and that encompass a broad range of cells and materials. The overall goal of this progress report is to highlight recent advances in 3D printing technologies that are helping to enable advances important in precision medicine.

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“…In adherent cells, several lines of evidence demonstrate how the effects of substrate rigidity on cytoskeletal architecture (mechanosensation) impacts cell behavior. Cell differentiation, spreading, actin stress fiber formation, and FA formation can be regulated by ECM rigidity . It is thus evident that the cytoskeleton can “feel” external rigidities, and alter cell morphology accordingly .…”

Section: The Cytoskeleton and Mechanosensitive Moleculesmentioning

confidence: 99%

“…Cell differentiation, spreading, actin stress fiber formation, and FA formation can be regulated by ECM rigidity. [49][50][51][52] It is thus evident that the cytoskeleton can "feel" external rigidities, and alter cell morphology accordingly. 5 Importantly, this change in the actin cytoskeleton following mechanical stress can directly impact cell signaling (mechanotransduction).…”

Section: The Cytoskeleton and Mechanosensitive Moleculesmentioning

confidence: 99%

Lymphocyte mechanotransduction: The regulatory role of cytoskeletal dynamics in signaling cascades and effector functions

Ben‐Shmuel¹,

Joseph²,

Sabag³

et al. 2019

Journal of Leukocyte Biology

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The process of mechanotransduction, that is, conversion of physical forces into biochemical signaling cascades, has attracted interest as a potential mechanism for regulating immune cell activation. The cytoskeleton serves a critical role in a variety of lymphocyte functions, from cellular activation, proliferation, adhesion, and migration, to creation of stable immune synapses, and execution of functions such as directed cytotoxicity. Though traditionally considered a scaffold that enables formation of signaling complexes that maintain stable immune synapses, the cytoskeleton was additionally shown to play a dynamic role in lymphocyte signaling cascades by sensing physical cues such as substrate rigidity, and transducing these mechanical features into chemical signals that ultimately influence lymphocyte effector functions. It is thus becoming clear that cytoskeletal dynamics are essential for the lymphocyte response, beyond the role of the cytoskeleton as a stationary framework. Here, we describe the transduction of extracellular forces to activate signaling pathways and effector functions mediated through the cytoskeleton in lymphocytes. We also highlight recent discoveries of cytoskeleton‐mediated mechanotransduction on intracellular signaling pathways in NK cells.

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Stem Cell Differentiation is Regulated by Extracellular Matrix Mechanics

Cited by 210 publications

References 100 publications

A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs

A Single Cell but Many Different Transcripts: A Journey into the World of Long Non-Coding RNAs

Recent Advances in Enabling Technologies in 3D Printing for Precision Medicine

Lymphocyte mechanotransduction: The regulatory role of cytoskeletal dynamics in signaling cascades and effector functions

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