Forces in stem cells and cancer stem cells

Chowdhury, Farhan; Huang, Bo; Wang, Ning

doi:10.1016/j.cdev.2022.203776

Cited by 8 publications

(5 citation statements)

References 211 publications

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“…Embryos that are null for fibronectin or α 5 β 1 integrins show distinct defects in mesodermal development [34,35]. In addition, fibronectin or fibronectin-mimicking RGD tripeptides-based mechanotransduction studies showed initiation of cell differentiation of mouse ESCs [21]. Furthermore, fibronectin has been shown to activate the ERK/ MAPK pathway to induce differentiation in mouse ESCs [16].…”

Section: Discussionmentioning

confidence: 99%

“…Traction stresses are an important parameter to determine stress-mediated cell differentiation of pluripotent cells [20]. The overall role of forces/stresses and force-mediated signaling in regulating the fate decisions of stem cells has been reviewed elsewhere in detail [21]. As predicted, the traction magnitude at the basal colony surface was found to be high at the periphery and low at the colony center (Figure 4A), which is consistent with the 3D confocal imaging data in Figures 3 and S4.…”

Section: Traction Stresses At the Colony Periphery Lead To Heterogene...mentioning

confidence: 99%

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Reduced Cell–ECM Interactions in the EpiSC Colony Center Cause Heterogeneous Differentiation

Amar

Saha

Debnath

et al. 2023

Cells

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Mechanoregulation of cell–extracellular matrix (ECM) interactions are crucial for dictating pluripotent stem cell differentiation. However, not all pluripotent cells respond homogeneously which results in heterogeneous cell populations. When cells, such as mouse epiblast stem cells (EpiSCs), are cultured in clusters, the heterogeneity effect during differentiation is even more pronounced. While past studies implicated variations in signaling pathways to be the root cause of heterogeneity, the biophysical aspects of differentiation have not been thoroughly considered. Here, we demonstrate that the heterogeneity of EpiSC differentiation arises from differences in the colony size and varying degrees of interactions between cells within the colonies and the ECM. Confocal imaging demonstrates that cells in the colony periphery established good contact with the surface while the cells in the colony center were separated by an average of 1–2 µm from the surface. Traction force measurements of the cells within the EpiSC colonies show that peripheral cells generate large tractions while the colony center cells do not. A finite element modeling of EpiSC colonies shows that tractions generated by the cells at the colony periphery lift off the colony center preventing the colony center from undergoing differentiation. Together, our results demonstrate a biophysical regulation of heterogeneous EpiSC colony differentiation.

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Section: Discussionmentioning

confidence: 99%

Section: Traction Stresses At the Colony Periphery Lead To Heterogene...mentioning

confidence: 99%

Reduced Cell–ECM Interactions in the EpiSC Colony Center Cause Heterogeneous Differentiation

Amar

Saha

Debnath

et al. 2023

Cells

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“…Human tissues are subjected to a diverse range of mechanical forces, including flow shear, compression, tension, osmotic pressure, myosin-mediated contraction, and gravitational forces [13,14]. Moreover, the mechanical properties of tissues themselves play a crucial role in cell growth, stem cell differentiation, cancer development, and even Alzheimer's disease [16,[233][234][235]. Additionally, diseases can also alter the mechanical properties of cells themselves.…”

Section: Cell and Tissue Mechanics In Normal And Aberrant Physiologymentioning

confidence: 99%

The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation

Nakamura

2024

IJMS

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Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research suggests that they may be regulated by both distinct and shared pathways. Specifically, recent studies have indicated that both CIP and CIL utilize mechanotransduction pathways, a process that involves cells sensing and responding to mechanical forces. This review article describes the role of mechanotransduction in CI, shedding light on how mechanical forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable of directly or indirectly binding to specific DNA sequences in distant genes to regulate gene expression, emerge as sensitive players in both the mechanotransduction and signaling pathways of CI. This article presents methods for identifying these TAF proteins and profiling the associated changes in chromatin structure, offering valuable insights into CI and other biological functions mediated by mechanotransduction. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions.

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“…Human tissues are subjected to a diverse range of mechanical forces, including flow shear, compression, tension, osmotic pressure, myosin-mediated contraction, and gravitational forces [12,13]. Moreover, the mechanical properties of tissues themselves play a crucial role in cell growth, stem cell differentiation, cancer development, and even Alzheimer's disease [15,[220][221][222]. Additionally, diseases can also alter the mechanical properties of cells themselves.…”

Section: Cell and Tissue Mechanics In Normal And Aberrant Physiologymentioning

confidence: 99%

Contact Inhibition and Mechanotransduction

Nakamura

2023

Preprint

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Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing the formation of cancerous tissues. CI can be further categorized into two distinct yet interrelated components: CI of locomotion (CIL) and CI of proliferation (CIP). These two components of CI have historically been viewed as separate processes, but emerging research indicates that they share both distinctive and common pathways. Moreover, they exhibit intriguing intersections with mechanotransduction, a process that involves cells sensing and responding to mechanical forces. This review article describes the intricate interplay between mechanical forces and CI, shedding light on how these forces regulate CIL and CIP. Emphasis is placed on filamin A (FLNA)-mediated mechanotransduction, elucidating how FLNA senses mechanical forces and translates them into crucial biochemical signals that regulate cell locomotion and proliferation. In addition to FLNA, trans-acting factors (TAFs) emerge as sensitive players in both CI and the mechanotransduction process. This article presents methods for identifying these TAFs and profiling the associated changes in chromatin structure, offering valuable insights into CI and mechanotransduction regulation. Finally, it addresses unanswered research questions in these fields and delineates their possible future directions.

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Forces in stem cells and cancer stem cells

Cited by 8 publications

References 211 publications

Reduced Cell–ECM Interactions in the EpiSC Colony Center Cause Heterogeneous Differentiation

Reduced Cell–ECM Interactions in the EpiSC Colony Center Cause Heterogeneous Differentiation

The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation

Contact Inhibition and Mechanotransduction

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