Understanding the mechanisms that specify and maintain the identities of more than 200 cell types of the human body is arguably one of the most fundamental problems in the field. Stem cells are located within each tissue of the body.
Stem cells have the ability to make a copy of themselves or mature into defined lineages when they divide. The work of a team led by biochemists at the University of California, Riverside has improved our understanding of how a specific lineage identity is maintained every time a stem cell divides.
The study led by Sihem Cheloufi and Jernej Murn shows how a complex of genes controls the organization of the genome. The report is in Nature Communications.
Each time a cell divides, it has to create a replica of its genome, not only its DNA sequence, but also how the DNA is packaged with proteins. There are either open and easily accessible or more densely packed and less accessible genomic sites.
The genes located in the more open parts of the genome can potentially become expressed and turned into proteins.
She said that to maintain cell identity during cell division, the locations of open and closed chromatin must be faithfully passed onto the new replica of the genome.
She said that a host of transcription factors are attracted to open regions in a DNA sequence-specific manner to serve as bookmarks and recruit transcription machinery to correct lineage-specific genes.
The authors looked at immature blood cells that can either self-renew or turn into neutrophils, which are non-dividing cells that present our body's first line of defense against pathogens. They found that it was essential for maintaining the self-renewal of these immature blood cells, but also for preserving their identity. The cells lost their identity and adopted a mixed lineage stage even after a moderate reduction of CAF-1 levels.
Stem cells that don't have CAF-1 become more plastic, co-expressing genes from different lineages, including those of red blood cells and platelets.
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We found a lot of genomic sites that are open and attract ELF1 as a result of the loss of CAF-1.
The immature blood cells were engineered for growth in tissue culture. They used a mouse model to confirm their findings and collaborated with a co-corresponding author on the study.
They would like to understand the mechanism by which the process of preserving the chromatin state is different for different cell types.
The genome has a landscape with specific landmarks. We expect the role of CAF-1 in packaging the genome to act as a general gateway to cellular identity. This would apply to all dividing cells across multiple tissues, including the brain.
More information: Regulation of Chromatin Accessibility by the Histone Chaperone CAF-1 Sustains Lineage Fidelity., Nature Communications (2022). DOI: 10.1038/s41467-022-29730-6 Journal information: Nature Communications Citation: Study identifies how blood stem cells maintain their fate (2022, April 29) retrieved 29 April 2022 from https://phys.org/news/2022-04-blood-stem-cells-fate.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
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