# Phenotypic plasticity and secretory heterogeneity in subpopulations derived from single cancer cell

## TL;DR

This paper introduces a new platform for studying single cancer cells to understand their behavior and response to drugs, which could lead to better cancer treatments.

## Contribution

A novel microfluidic platform enables long-term single-cell culture and analysis of phenotypic plasticity and secretory heterogeneity.

## Key findings

- Single-cell cultures maintain phenotypic equilibria similar to their parental populations.
- Chemotherapy disrupts this balance, favoring stem-like cells with enhanced signaling and survival gene expression.
- The platform can be used to study complex phenotypes and drug responses in cancer cells.

## Abstract

Single-cell analysis of phenotypic plasticity could improve the development of more effective therapeutics. Still, the development of tools to measure single-cell heterogeneity has lagged due to difficulties in manipulating and culturing single cells. Here, we describe a single-cell culture and phenotyping platform that employs a starburst microfluidic network and automatic liquid handling system to capture single cells for long-term culture and multi-dimensional analysis and quantify their clonal properties via their surface biomarker and secreted cytokine/growth factor profiles. Studies performed on this platform found that cells derived from single-cell cultures maintained phenotypic equilibria similar to their parental populations. Single-cell cultures exposed to chemotherapeutic drugs stochastically disrupted this balance to favor stem-like cells. They had enhanced expression of mRNAs and secreted factors associated with cell signaling, survival, and differentiation. This single-cell analysis approach can be extended to analyze more complex phenotypes and screen responses to therapeutic targets.

A starburst microfluidic chip was designed for achieving single-cell capture, proliferation, secretion, staining, and recovery to study the phenotypic equilibria among single-cell derived subpopulations.Image 1