The Beane Lab

Stem Cells, Regeneration & Morphogenesis
in the age of Quantum Biology

Beane Lab planarian worm
Wound Epithelium

Wound Epithelium

F-actin (green) and nuclear (blue) staining reveals the morphology of the wound edge.

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Research Project 1

ROS Signaling

After injury, how does an animal “know” to start regenerating the missing tissues?

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ROS signaling - control trunk fragment of a recently amputated planarian labelled with a dye that marks ROS accumulation

Above: Control trunk fragment of a recently amputated planarian labelled with a dye that marks ROS accumulation.

After injury, how does an animal “know” to start regenerating the missing tissues? We wonder about this too! We are researching one of the very first signals identified after injury: reactive oxygen species (ROS).

Our Research:

We are interested in determining the signals that initiate regeneration and tissue repair. Signaling downstream of reactive oxygen species (ROS) is known to regulate stem cell fate decisions, and ROS accumulation occurs at the wound site immediately after an injury. ROS are byproducts of aerobic metabolism that are highly reactive, and include molecules like superoxide and the second messenger hydrogen peroxide.

Our data shows that ROS signaling is required for the downstream expression of genes, such as the heat shock protein Hsp70, that are required for the stem cell proliferative response that follows injury in planarians. Without this signaling, the new tissues of the blastema do not grow and regeneration is inhibited. We are currently investigating the mechanisms (both upstream and downstream of ROS) that are involved.
Stem Cell Division
Normal
Blocked
Control and ROS-Inhibited regenerating planarians labelled for actively dividing stem cells

Above: Control (on left) and ROS-Inhibited (on right) regenerates labelled for actively dividing stem cells (green) reveal that ROS are required for new growth.

Summary

ROS are short-lived molecules produced at the wound site immediately after injury. They act as critical second messengers initiating the cascade of events required for stem cell activation and new tissue growth.

Methods

Fluorescent ROS reporters, live imaging, pharmacological inhibitors (DPI, NAC), and RNAi knockdown in planarians to dissect temporal and spatial regulation of ROS during wound healing and blastema formation.

Significance

Understanding how ROS coordinates stem cell proliferation could inform therapies for non-healing wounds and cancer, where ROS signaling is often dysregulated.

Related Publications

1

Van Huizen, A.V., Morton, J.M.G., Kinsey, L.J., Von Kannon, D.G., Saad, M.A., Bhatt, T.R., Feldman, J.M., Gerecht, J., and Beane, W.S. (2019). Weak magnetic fields alter stem cell–mediated growth. Science Advances 5(1).

2

Beane, W.S., Morokuma, J., Adams, D.S., Levin, M. (2011). A Chemical Genetics Approach Reveals H,K-ATPase-Mediated Membrane Voltage Is Required for Planarian Head Regeneration. Chemistry & Biology 18(1):77–89.

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