Genome complexity in embryology: stem cell action (Introduction)

by David Turell , Friday, July 28, 2017, 19:20 (2676 days ago) @ David Turell

This careful and complex study follows stem cells as they differentiate. They make decisions along the way:

http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2001867

Abstract

"Individual cells take lineage commitment decisions in a way that is not necessarily uniform. We address this issue by characterising transcriptional changes in cord blood-derived CD34+ cells at the single-cell level and integrating data with cell division history and morphological changes determined by time-lapse microscopy. We show that major transcriptional changes leading to a multilineage-primed gene expression state occur very rapidly during the first cell cycle. One of the 2 stable lineage-primed patterns emerges gradually in each cell with variable timing. Some cells reach a stable morphology and molecular phenotype by the end of the first cell cycle and transmit it clonally. Others fluctuate between the 2 phenotypes over several cell cycles. Our analysis highlights the dynamic nature and variable timing of cell fate commitment in hematopoietic cells, links the gene expression pattern to cell morphology, and identifies a new category of cells with fluctuating phenotypic characteristics, demonstrating the complexity of the fate decision process (which is different from a simple binary switch between 2 options, as it is usually envisioned)."

Author summary

"Hematopoietic stem cells are classically defined as a specific category of cells at the top of the hierarchy that can differentiate all blood cell types following step-by-step the instructions of a deterministic program. We have analysed this process, and our findings support a much more dynamic view than previously described. We apply time-lapse microscopy coupled to single-cell molecular analyses in human hematopoietic stem cells and find that fate decision is not a unique, programmed event but a process of spontaneous variation and selective stabilisation reminiscent of trial–error processes. We show that each cell explores (at its own pace and independently of cell division) many different possibilities before reaching a stable combination of genes to be expressed. Our results suggest, therefore, that multipotency seems to be more like a transitory state than a feature of a specific cell category."

A simpler take:

https://cosmosmagazine.com/biology/becoming-a-cell

"At every moment from fertilisation onwards the creation of a human body requires cells, generated by cell division, to “choose” which of the many possible kinds of cell they will become. How do they decide?

"One common view is that there was some step-by-step decision-making process or algorithm to follow. New research from a team of French biologists led by Alice Moussy of the Ecole Pratique des Hautes Etudes suggests that this is not the case.

"The researchers microscopic video recordings and single-cell molecular analyses to observe the process of hematopoietic stem cells (cells which can become any one of a number of different kinds of blood cell). They discovered that rather than a single decision event, cell specialisation was a dynamic process involving spontaneous fluctuations between alternative cell states and selective stabilisation of certain states.

"In a sense it is a trial-and-error process: each cell independently “tries out” different molecular possibilities – via turning on and off different genes – before settling into a stable state of activated genes and a corresponding shape."

Comment: Stem cells seem in this study to have trouble making up their 'minds', but it all works out in the end with 9usually) all the cells in all the right places. The cells are influenced also by mechanical forces from other cells as well as hormonal and chemical signals. As the result they are buffeted in may ways as the embryo develops. All of these ways are still being actively studied since making a fully developed individual is not fully understood. The underlying process is one automatic system: all newborns look generally alike.