Burning fat to make mature blood cells

In fruit flies, the breakdown of fatty acids may drive the maturation of blood cells.

Fruit fly larvae showing blood progenitors (marked in cyan) with fat droplets (shown in yellow). The nucleus (which contains the DNA) is marked in magenta. Image credit: Satish Kumar Tiwari (CC BY 4.0)

Stem cells are special precursor cells, found in all animals from flies to humans, that can give rise to all the mature cell types in the body. Their job is to generate supplies of new cells wherever these are needed. This is important because it allows damaged or worn-out tissues to be repaired and replaced by fresh, healthy cells.

As part of this renewal process, stem cells generate pools of more specialized cells, called progenitor cells. These can be thought of as half-way to maturation and can only develop in a more restricted number of ways. For example, so-called myeloid progenitor cells from humans can only develop into a specific group of blood cell types, collectively termed the myeloid lineage.

Fruit flies, like many other animals, also have several different types of blood cells. The fly’s repertoire of blood cells is very similar to the human myeloid lineage, and these cells also develop from the fly equivalent of myeloid progenitor cells. These progenitors are found in a specialized organ in fruit fly larvae called the lymph gland, where the blood forms. These similarities between fruit flies and humans mean that flies are a good model to study how myeloid progenitor cells mature.

A lot is already known about the molecules that signal to progenitor cells how and when to mature. However, the role of metabolism – the chemical reactions that process nutrients and provide energy inside cells – is still poorly understood. Tiwari et al. set out to identify which metabolic reactions myeloid progenitor cells require and how these reactions might shape the progenitors’ development into mature blood cells.

The experiments in this study used fruit fly larvae that had been genetically altered so that they could no longer perform key chemical reactions needed for the breakdown of fats. In these mutant larvae, the progenitors within the lymph gland could not give rise to mature blood cells. This showed that myeloid progenitor cells need to be able to break down fats in order to develop properly.

These results highlight a previously unappreciated role for metabolism in controlling the development of progenitor cells. If this effect also occurs in humans, this knowledge could one day help medical researchers engineer replacement tissues in the lab, or even increase our own bodies’ ability to regenerate blood, and potentially other organs.