2022-05-12| R&D

New Kind of Cell Division Without DNA Replication

by GeneOnline
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DNA replication has long been recognized as a key component of somatic cell proliferation, but a team of researchers at Academia Sinica Taiwan accidentally discovered an atypical cell division mechanism in zebrafish epidermal cells that can divide without DNA replication. Since this discovery represents a breakthrough in the understanding of cell division over the past century, the research has recently been published in Nature and promoted as a special article.

Related article: The Era of Enzymatic DNA Synthesis: How Can DNA Printing Be Useful for Research?


A Temporary Solution for Rapid Growth: Proliferation Without DNA Replication


This groundbreaking study was published by the team of Dr. Chen Chen-Hui, Assistant Research Fellow at the Institute of Cell and Organismal Biology of Academia Sinica. The team originally intended to explore the cellular and molecular mechanisms of the biological regeneration process through superficial epithelial cells (SECs) in zebrafish, but accidentally observed substantial division of epithelial cells during the process. Since this new mode of cell division does not require DNA replication, it has been named “asynthetic fission”.

However, as convenient as it may seem, the process without DNA replication may still pose many problems for the progeny cells. The team indeed noticed some special cases during their observations, such as incomplete DNA partitioning or even failure to divide, which made the researchers even more curious about the reason behind the asynthetic fission.

Dr. Chen believes that asynthetic fission may be a temporary solution for epithelial cells, aiming only at responding quickly to maintain sufficient epithelial coverage during rapid growth. The team created a multicolor cell membrane tagging system, palmskin, to monitor the entire population of superficial epithelial cells (SECs) in developing zebrafish larvae.

Using time-lapse imaging, the team discovered that asynthetic fission indeed peaked during the rapid growth stage of larval development. During this period, a single SEC can produce a maximum of four progeny cells. They even found that these terminally differentiated skin cells continue splitting despite an absence of DNA replication. Although these progeny cells are smaller, flatter, and do not have intact DNA, they provide greater epithelial coverage. As the growth of the animal becomes more stable over the weeks, these “temporary workers” that do not carry intact DNA are gradually replaced by normal cells.

Mechanism of Asynthetic Fission Remains to Be Explored


Dr. Chen’s team speculated that asynthetic fission may be controlled mainly by dynamic changes in epidermal tension during organismal growth. Subsequent experiments on the ion channel protein Piezo1 showed that asynthetic fission was enhanced by stimulating Piezo1 and diminished by inhibiting Piezo1 gene expression. In addition, the team also tried to control the growth rate of zebrafish larvae by rearing them at different densities and also found that the rate of asynthetic fission in epithelial cells changed.

It is worth mentioning that the team also noticed that the larvae with Piezo1 suppression still exhibited normal body growth rate. It will be intriguing to investigate whether progenitor cells in the basal laminae divide more due to compensatory mechanisms or other adaptive growth mechanisms. Analysis through genetic engineering techniques may help to determine whether the mode of asynthetic fission is truly independent of cell cycle regulation and checkpoint mechanisms.

Even though many questions remain to be answered, Dr. Chen believes that asynthetic fission, as a low-cost and highly flexible cell division pattern, may not only occur in zebrafish epithelial cells. Nevertheless, the current understanding of anaplastic division is still quite limited, thus in-depth exploration of the underlying mechanisms will be the focus of future research.

Written by Nana Ho, Translated by Richard Chau

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