split or not? Individual cells make decisions much more autonomously than previously thought.

Cells make choices based not only on external signals such as growth factors, but also on information received from within the cell.

Humans make choices every day. These decisions often require a combination of various contextual cues to ensure that decisions are made that are appropriate to the situation. Our senses provide us with the wealth of knowledge we need to make decisions. They pick up specific details about our surroundings, such as visual and auditory information, and the brain combines them to build a holistic perception.This is known as multisensory or multimodal perception. .

Cells take their own state into account when making choices

In this regard, individual cells are similar to humans. They always make important decisions, such as whether to split up. Researchers at the University of Zurich (UZH) have therefore extended the concept of contextual and multimodal perception found in humans to individual cells. Surprisingly, scientists have discovered that single cells make decisions much more autonomously than previously thought.

“Good decision-making by individual cells uses multimodal perception to enable cells to integrate external signals, such as growth factors, with information from within the cell, such as the number of organelles.” says Lucas Pelkmans. Pelkmans is a professor in the Department of Molecular Life Sciences at UZH.

In some cases, such internal cues can override external stimuli. For example, in tumors, the actual state of certain cells overrides treatment with antiproliferative drugs, rendering them refractory. “Such drug resistance is a major problem in the fight against cancer. Solutions may come from taking into account the contextual cues experienced by individual cells and ultimately altering them.” There is,” he says Pelkmans.

Simultaneously analyze dozens of proteins in millions of cells

To test whether cells make decisions according to contextual and multimodal perceptions, as humans do, scientists will study the activity of multiple signaling nodes (external sensors of the cell) and the local environment and/or cell microenvironment. number of organs. All had to be analyzed in single cells and across millions of cells. “To do this, we used the method ‘4i’ developed at UZH. This allows simultaneous visualization and quantification of up to 80 different proteins and protein modifications within a single cell using fluorescence microscopy. study.

Researchers have found that the variability in the activity of individual sensors across cells is closely related to the variation in internal cues. For example, the amount of mitochondria, the powerhouses of cells, fundamentally affects how individual cells perceive external stimuli. Additionally, each sensor integrates different cues from within the cell. When researchers evaluated a key decision for single cells: whether to proliferate or remain quiescent in response to a growth stimulus, cell selection was mediated by the perception of multiple sensors, which provide clues to the cell’s internal state. was found to be predictably modulated by

Cells make intelligent decisions

“In order for a cell to make a specific decision, it needs to look at all external signals and internal cues simultaneously. We are definitely smarter than we were before,” said Ph.D. Cramer Candidate.

See: “Multimodal Perception Links Cell State to Single Cell Decision Making,” Bernhard A. Kramer, Jacobo Sarabia del Castillo, Lucas Pelkmans, 14 July 2022 chemistry.
DOI: 10.1126/science.abf4062