Modulation of corneal tissue mechanics influences epithelial cell phenotype

SummaryWhilst the control of stem cell differentiation using substrates of differing compliance has been extensively explored in vitro, the significance of this mechanism at a physiological level is not known. Here we set to explore the role of corneal surface biomechanics in controlling epithelial cell proliferation and differentiation. Using non-contact high-resolution Brillouin spectro-microscopy we showed that the corneal outer edge (limbus) has significantly lower bulk modulus compared to the central cornea, and that this difference is precisely delimited in the organ. Furthermore, the areas of the limbus with distinctly softer properties were shown to be associated with limbal epithelial stem cell (LESC) residence. Based on these findings, we then provided the first demonstration of the capacity to modulate LESC phenotype, both in vivo and ex vivo, solely through the recreation/restoration of suitable biomechanical niches. These results thus confirm the fundamental role of corneal biomechanics in directing epithelial stem cell behavior.

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Geometry alone influences stem cell differentiation in a precision 3D printed stem cell niche:

10.1101/489773 ◽

2018 ◽

Author(s):

Elisabetta Prina ◽

Laura Sidney ◽

Maximilian Tromayer ◽

Jonathan Moore ◽

Robert Liska ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Niche ◽

Stem Cell Differentiation ◽

Cell Phenotype ◽

Cell Therapies ◽

Epithelial Stem Cell ◽

Signalling Molecules ◽

Two Photon ◽

3D Printed ◽

Cell Niche

Stem cells within epithelial tissues reside in anatomical structures known as crypts that are known to contribute to the mechanical and chemical milieu important for function. To date, epithelial stem cell therapies have largely ignored the niche and focussed solely on the cell population to be transplanted. Our aim was to recreate the precise geometry of the epithelial stem cell niche using two photon polymerisation and to determine the influence of this structure alone on stem cell phenotype. We were able to recreate crypt structures and following cell seeding, a zonation in cell phenotype along the z-axis emerged. This illustrates that geometry alone, without the use of exogenous signalling molecules, influences cell response. Understanding the role of geometry in the regulation of the stem cell niche will enable significant advances in our ability to influence stem cell behaviour to expedite cellular therapies to the clinic.

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HIV Type 1 Alters Mesenchymal Stem Cell Differentiation Potential and Cell Phenotype ex Vivo

AIDS Research and Human Retroviruses ◽

10.1089/aid.2010.0114 ◽

2011 ◽

Vol 27 (2) ◽

pp. 187-199 ◽

Cited By ~ 33

Author(s):

Eoin J. Cotter ◽

Nicholas Chew ◽

William G. Powderly ◽

Peter P. Doran

Keyword(s):

Stem Cell ◽

Cell Differentiation ◽

Mesenchymal Stem Cell ◽

Ex Vivo ◽

Stem Cell Differentiation ◽

Cell Phenotype ◽

Differentiation Potential ◽

Mesenchymal Stem Cell Differentiation ◽

Hiv Type 1

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The role of AMPK pathway in mediating the effects of metformin on mesenchymal stem cell differentiation

Bone Abstracts ◽

10.1530/boneabs.4.p166 ◽

2015 ◽

Author(s):

Suet Ching Chen ◽

Rebecca Brooks ◽

Syed Faisal Ahmed ◽

Stephen J Yarwood

Keyword(s):

Stem Cell ◽

Cell Differentiation ◽

Mesenchymal Stem Cell ◽

Stem Cell Differentiation ◽

Ampk Pathway ◽

Mesenchymal Stem Cell Differentiation

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Role of Signaling Pathways in Mesenchymal Stem Cell Differentiation

Current Stem Cell Research & Therapy ◽

10.2174/1574888x09666140812112002 ◽

2014 ◽

Vol 9 (6) ◽

pp. 508-512 ◽

Cited By ~ 19

Author(s):

Birru Bhaskar ◽

Naveen Mekala ◽

Rama Baadhe ◽

Parcha Rao

Keyword(s):

Stem Cell ◽

Cell Differentiation ◽

Mesenchymal Stem Cell ◽

Signaling Pathways ◽

Stem Cell Differentiation ◽

Mesenchymal Stem Cell Differentiation

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Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification

Blood ◽

10.1182/blood-2011-01-328567 ◽

2011 ◽

Vol 118 (5) ◽

pp. 1264-1273 ◽

Cited By ~ 47

Author(s):

Melanie G. Cornejo ◽

Vinciane Mabialah ◽

Stephen M. Sykes ◽

Tulasi Khandan ◽

Cristina Lo Celso ◽

...

Keyword(s):

Stem Cell ◽

Notch Signaling ◽

Signaling Pathway ◽

Hematopoietic Stem Cell ◽

Stem Cell Differentiation ◽

Notch Signaling Pathway ◽

Developmental Pathways ◽

Lineage Specification ◽

Hematopoietic Stem

Abstract The NOTCH signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. However, the molecular basis for its role at the different steps of stem cell lineage commitment is unclear. We recently identified the NOTCH signaling pathway as a positive regulator of megakaryocyte lineage specification during hematopoiesis, but the developmental pathways that allow hematopoietic stem cell differentiation into the erythro-megakaryocytic lineages remain controversial. Here, we investigated the role of downstream mediators of NOTCH during megakaryopoiesis and report crosstalk between the NOTCH and PI3K/AKT pathways. We demonstrate the inhibitory role of phosphatase with tensin homolog and Forkhead Box class O factors on megakaryopoiesis in vivo. Finally, our data annotate developmental mechanisms in the hematopoietic system that enable a decision to be made either at the hematopoietic stem cell or the committed progenitor level to commit to the megakaryocyte lineage, supporting the existence of 2 distinct developmental pathways.

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