TY - JOUR
T1 - Inference of cell mechanics in heterogeneous epithelial tissue based on multivariate clone shape quantification
AU - Tsuboi, Alice
AU - Umetsu, Daiki
AU - Kuranaga, Erina
AU - Fujimoto, Koichi
N1 - Funding Information:
We thank K. Matsushita and K. Hironaka for discussions; Dr. S. Hayashi, Dr. Y. Hong, Dr. H. Sink, and the Bloomington Drosophila Stock Center for fly stocks; N. Iijima, T. Iwatsuki, and S. Hoshika for the hand-correction of the segmentation of experimental images; S. Fujita, H. Furukawa, R. Hara, K. Ikeguchi, and Y. Tanaka for participating the segmentation error estimation test. AT is a JSPS Research Fellow (15J01837). This work was supported by Grants-in-Aid for Scientific Research from MEXT to DU (15K18536, 17K07402, 17H02939), EK (JP26114003, JP16H04800, 17K19884), and KF (15H01490, 17H05619).
PY - 2017/8/3
Y1 - 2017/8/3
N2 - Cell populations in multicellular organisms show genetic and non-genetic heterogeneity, even in undifferentiated tissues of multipotent cells during development and tumorigenesis. The heterogeneity causes difference of mechanical properties, such as, cell bond tension or adhesion, at the cell-cell interface, which determine the shape of clonal population boundaries via cell sorting or mixing. The boundary shape could alter the degree of cell-cell contacts and thus influence the physiological consequences of sorting or mixing at the boundary (e.g., tumor suppression or progression), suggesting that the cell mechanics could help clarify the physiology of heterogeneous tissues. While precise inference of mechanical tension loaded at each cell-cell contacts has been extensively developed, there has been little progress on how to distinguish the population-boundary geometry and identify the cause of geometry in heterogeneous tissues. We developed a pipeline by combining multivariate analysis of clone shape with tissue mechanical simulations. We examined clones with four different genotypes within Drosophila wing imaginal discs: wild-type, tartan (trn) overexpression, hibris (hbs) overexpression, and Eph RNAi. Although the clones were previously known to exhibit smoothed or convoluted morphologies, their mechanical properties were unknown. By applying a multivariate analysis to multiple criteria used to quantify the clone shapes based on individual cell shapes, we found the optimal criteria to distinguish not only among the four genotypes, but also non-genetic heterogeneity from genetic one. The efficient segregation of clone shape enabled us to quantitatively compare experimental data with tissue mechanical simulations. As a result, we identified the mechanical basis contributed to clone shape of distinct genotypes. The present pipeline will promote the understanding of the functions of mechanical interactions in heterogeneous tissue in a non-invasive manner.
AB - Cell populations in multicellular organisms show genetic and non-genetic heterogeneity, even in undifferentiated tissues of multipotent cells during development and tumorigenesis. The heterogeneity causes difference of mechanical properties, such as, cell bond tension or adhesion, at the cell-cell interface, which determine the shape of clonal population boundaries via cell sorting or mixing. The boundary shape could alter the degree of cell-cell contacts and thus influence the physiological consequences of sorting or mixing at the boundary (e.g., tumor suppression or progression), suggesting that the cell mechanics could help clarify the physiology of heterogeneous tissues. While precise inference of mechanical tension loaded at each cell-cell contacts has been extensively developed, there has been little progress on how to distinguish the population-boundary geometry and identify the cause of geometry in heterogeneous tissues. We developed a pipeline by combining multivariate analysis of clone shape with tissue mechanical simulations. We examined clones with four different genotypes within Drosophila wing imaginal discs: wild-type, tartan (trn) overexpression, hibris (hbs) overexpression, and Eph RNAi. Although the clones were previously known to exhibit smoothed or convoluted morphologies, their mechanical properties were unknown. By applying a multivariate analysis to multiple criteria used to quantify the clone shapes based on individual cell shapes, we found the optimal criteria to distinguish not only among the four genotypes, but also non-genetic heterogeneity from genetic one. The efficient segregation of clone shape enabled us to quantitatively compare experimental data with tissue mechanical simulations. As a result, we identified the mechanical basis contributed to clone shape of distinct genotypes. The present pipeline will promote the understanding of the functions of mechanical interactions in heterogeneous tissue in a non-invasive manner.
KW - Cell mechanics
KW - Cell mixing
KW - Cell sorting
KW - Drosophila
KW - Heterogeneity
KW - PCA
KW - Tumor
KW - Vertex model
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U2 - 10.3389/fcell.2017.00068
DO - 10.3389/fcell.2017.00068
M3 - Article
AN - SCOPUS:85026831296
VL - 5
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
SN - 2296-634X
IS - AUG
M1 - 68
ER -