What makes stem cells decide whether they should make more stem cells or differentiate into other cells? According to researchers at New York’s Rockefeller University, it is the distribution of organelles – the tiny structures present in the cytoplasm of cells such as mitochondria, vacuoles, nuclei, and peroxisomes. The researchers showed that the positioning and balance of the peroxisomes appear to play a pivotal role in the fate of the stem cells.
The researchers looked at skin cells in the epidermis – the outer layer of the skin. Stem cells are located deep within the epidermis. During development the stem cells divide. Amma Asare, first author for the study, explained that the “cells divide so that one renewing stem cell daughter remains inward while the other daughter differentiates and moves outward to become part of the epidermis’ outer layers.” The team investigated how stem cells begin the transition.
The team looked mouse skin as it developed and used an approach that allowed them to look at genes that help to determine whether cells remain stem-cell like or whether they differentiate into other cell types. During the research, a protein called Pex11b was studied. Pex11b is a protein associated with the membrane of the peroxisome. The protein appeared to be involved in making sure that the peroxisomes of the cell are in the correct position ready for cell division.
In cells that lacked Pex11b, the peroxisomes were not split evenly between the daughter cells – for instance, one cell may receive all of the peroxisomes. When that was the case, cell division was slowed and the mitotic spindle didn’t align properly. The team noted that disrupting Pex11b resulted in fewer cells that were able to differentiate into mature skin cells.
The team also used a technique that allowed them to manipulate the peroxisomes and move them around the inside of the cell to distribute them unevenly. The team found this also slowed down cell division. Peroxisome manipulation also prevented mouse embryos from developing normal skin.
The balance between renewal and differentiation must be carefully controlled, but the exact process by which that balance is achieved is unknown. However, the positioning of organelles is one of the factors that influences the fate of the cells. Senior author elaine Fuchs, said “While some evidence already suggested the distribution of organelles, including energy-producing mitochondria, can influence the outcome of cell division, we have shown for the first time that this phenomenon is essential to the proper behavior of stem cells and formation of the tissue.”