Biophysical informatics reveals distinctive phenotypic signatures and functional diversity of single-cell lineages DOI Creative Commons
Trevor Chan, Xingjian Zhang, Michael Mak

et al.

Bioinformatics, Journal Year: 2022, Volume and Issue: 39(1)

Published: Dec. 28, 2022

In this work, we present an analytical method for quantifying both single-cell morphologies and cell network topologies of tumor populations use it to predict 3D behavior.We utilized a supervised deep learning approach perform instance segmentation on label-free live images across wide range densities. We measured shape properties characterized 136 clones (SCCs) derived from the YUMM1.7 YUMMER1.7 mouse melanoma lines. Using unsupervised clustering algorithm, identified six distinct morphological subclasses. further observed differences in growth invasion dynamics subclasses vitro spheroid model. Compared existing methods 2D or phenotype, our requires less time, needs no specialized equipment, is capable much higher throughput, making ideal applications such as high-throughput drug screening clinical diagnosis.//github.com/trevor-chan/Melanoma_NetworkMorphology.Bioinformatics online.

Language: Английский

Single-cell technologies: From research to application DOI
Lu Wen, Guoqiang Li, Tao Huang

et al.

The Innovation, Journal Year: 2022, Volume and Issue: 3(6), P. 100342 - 100342

Published: Oct. 18, 2022

Language: Английский

Citations

84
The epithelial–mesenchymal plasticity landscape: principles of design and mechanisms of regulation DOI
Jef Haerinck, Steven Goossens, Geert Berx

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(9), P. 590 - 609

Published: May 11, 2023

Language: Английский

Citations

68
Compressive stresses in cancer: characterization and implications for tumour progression and treatment DOI

Julia A Linke,

Lance L. Munn, Rakesh K. Jain

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(11), P. 768 - 791

Published: Oct. 10, 2024

Language: Английский

Citations

11
Topology and Nuclear Size Determine Cell Packing on Growing Lung Spheroids DOI Creative Commons
Wenhui Tang, Jessie Huang, Adrian F. Pegoraro

et al.

Physical Review X, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 21, 2025

Within multicellular living systems, cells coordinate their positions with spatiotemporal accuracy to form various tissue structures and control development. These arrangements can be regulated by geometry, biochemical cues, as well mechanical perturbations. However, how pack during dynamic three-dimensional architectures formation remains unclear. Here, examining a growing spherical system, human lung alveolospheres, we observe an emergence of hexagonal packing order structural transition that comprise the epithelium. Surprisingly, cell behavior on surface alveolospheres resembles hard-disks spheres, where less deformable nuclei act effective “hard disks” prevent from getting too close. Nucleus-to-cell size ratio increases spheroids growth; result, find more hexagon-concentrated cellular increasing bond orientational order. Furthermore, osmotically changing compactness ordered when nucleus-to-cell increases, vice versa. characteristics are consistent reduced dynamics, together suggesting better stabilizes local neighborhoods may regulate complex biological functions such maturation morphogenesis. Published American Physical Society 2025

Language: Английский

Citations

1
Epigenetic memory acquired during long-term EMT induction governs the recovery to the epithelial state DOI Open Access
Paras Jain,

Sophia Corbo,

Kulsoom Mohammad

et al.

Journal of The Royal Society Interface, Journal Year: 2023, Volume and Issue: 20(198)

Published: Jan. 1, 2023

Epithelial–mesenchymal transition (EMT) and its reverse mesenchymal–epithelial (MET) are critical during embryonic development, wound healing cancer metastasis. While phenotypic changes short-term EMT induction reversible, long-term has been often associated with irreversibility. Here, we show that seen in MCF10A cells upon by TGF β need not be irreversible, but have relatively longer time scales of reversibility than those induction. Next, using a phenomenological mathematical model to account for the chromatin-mediated epigenetic silencing miR-200 family ZEB family, highlight how memory gained can slow recovery epithelial state post-TGF withdrawal. Our results suggest modifiers govern extent scale advise caution against labelling as ‘irreversible’.

Language: Английский

Citations

18
Increased heterogeneity in expression of genes associated with cancer progression and drug resistance DOI Creative Commons

Anwesha Bose,

Subhasis Datta, R. Mandal

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 41, P. 101879 - 101879

Published: Jan. 22, 2024

Fluctuations in the number of regulatory molecules and differences timings molecular events can generate variation gene expression among genetically identical cells same environmental condition. This variation, termed as noise, create metabolic state cellular functions, leading to phenotypic heterogeneity. Expression noise heterogeneity have been recognized important contributors intra-tumor heterogeneity, associated with cancer growth, progression, therapy resistance. However, how changes progression actual patients has remained poorly explored. Such an analysis, through identification genes increasing provide valuable insights into generation could implications for understanding immune-suppression, drug tolerance In this work, we performed a genome-wide using single-cell RNA-seq data lung adenocarcinoma at different stages cancer. We identified 37 epithelial that showed trend many which were also EMT found several these was positively mitochondrial genes, suggesting role mitochondria addition, uncovered substantial sample-specific profiles personalized prognosis treatment.

Language: Английский

Citations

6
Cell compression – relevance, mechanotransduction mechanisms and tools DOI
Laura M. Faure, Valeria Venturini, Pere Roca‐Cusachs

et al.

Journal of Cell Science, Journal Year: 2025, Volume and Issue: 138(6)

Published: March 15, 2025

ABSTRACT From border cell migration during Drosophila embryogenesis to solid stresses inside tumors, cells are often compressed physiological and pathological processes, triggering major responses. Cell compression can be observed in vivo but also controlled vitro through tools such as micro-channels or planar confinement assays. Such have recently become commercially available, allowing a broad research community tackle the role of variety contexts. This has led discovery conserved compression-triggered modes, fate determinants mechanosensitive pathways, among others. In this Review, we will first address different ways which their biological Then, discuss distinct mechanosensing mechanotransducing pathways that activate response compression. Finally, describe systems been engineered compress cells.

Language: Английский

Citations

0
Softness or Stiffness What Contributes to Cancer and Cancer Metastasis? DOI Creative Commons
Claudia Tanja Mierke

Cells, Journal Year: 2025, Volume and Issue: 14(8), P. 584 - 584

Published: April 12, 2025

Beyond the genomic and proteomic analysis of bulk single cancer cells, a new focus research is emerging that based on mechanical cells. Therefore, several biophysical techniques have been developed adapted. The characterization like human cell lines, started with their at mostly timepoint. A universal hypothesis has proposed cells need to be softer migrate invade tissues subsequently metastasize in targeted organs. Thus, softness suggested serve as physical marker for malignancy types. However, it turned out there exists opposite phenomenon, namely stiffer are more migratory invasive therefore lead metastases. These contradictory results question universality role malignant progression cancers. Another problem various used can affect properties making even difficult compare different studies. Apart from instrumentation, culture measurement conditions influence measurements. review highlights main advances discusses strength weaknesses approaches, questions whether passive still state-of-the art. Besides models, setups, microenvironment characteristics presented debated. Finally, combinatorial approaches determine potential tumors, such involvement ECM, homogeneous or heterogeneous association, biological multi-omics analyses, together dynamic-mechanical highlighted frontiers research.

Language: Английский

Citations

0
Protocol to encapsulate cerebral organoids with alginate hydrogel shell to induce volumetric compression DOI Creative Commons
Zitian Wang, Xiaowei Tang, Davit Khutsishvili

et al.

STAR Protocols, Journal Year: 2024, Volume and Issue: 5(2), P. 102952 - 102952

Published: March 29, 2024

In vitro organoids, including cerebral are usually developed without mechanical compression, which may contribute to a delay in maturation. Here, we present protocol for encapsulating organoids with thin shell of low-concentration alginate hydrogel. We describe steps organoid generation, microfluidic chip culture, Matrigel coating, expansion and encapsulation. then detail procedures maturation culture characterization. The moderate compressive stimulation that the provides promotes cell proliferation neuronal For complete details on use execution this protocol, please refer Tang et al.1

Language: Английский

Citations

3
Living in a noisy world—origins of gene expression noise and its impact on cellular decision‐making DOI Open Access
Sampriti Pal, Riddhiman Dhar

FEBS Letters, Journal Year: 2024, Volume and Issue: 598(14), P. 1673 - 1691

Published: May 9, 2024

The expression level of a gene can vary between genetically identical cells under the same environmental condition—a phenomenon referred to as noise. Several studies have now elucidated central role transcription factors in generation Transcription factors, key components regulatory networks, drive many important cellular decisions response and signals. Therefore, very relevant question is how noise impacts regulation influences decision‐making. In this Review, we summarize current understanding molecular origins noise, highlighting process, discuss ways which influence As advances single‐cell technologies open new avenues for studying well circuits, better on will implications biological processes.

Language: Английский

Citations

3