A Bruno-like gene is required for stem cell maintenance in planarians

Area of Science:

• Stem cell biology
• Regenerative medicine
• Molecular biology

Background:

• Freshwater planarians possess remarkable regenerative abilities driven by pluripotent stem cells known as neoblasts.
• Neoblast maintenance is crucial for continuous regeneration throughout the organism's lifespan.

Purpose of the Study:

• To investigate the role of RNA binding proteins in regulating planarian neoblasts.
• To identify specific factors critical for neoblast self-renewal and maintenance.

Main Methods:

• RNA interference (RNAi) was used to knockdown the Smed-bruno-like (bruli) gene in Schmidtea mediterranea planarians.
• Immunohistochemistry with antibodies against SMEDWI-1 and Histone H4 (monomethyl-K20), along with cell-cycle markers, was employed to analyze neoblast populations.
• Wound-healing and regeneration assays were performed after bruli knockdown.

Main Results:

• bruli mRNA and protein are expressed in neoblasts and the central nervous system.
• bruli knockdown led to the elimination of detectable Bruli protein, resulting in a dramatic reduction or elimination of neoblasts.
• Planarians with bruli knockdown initiated blastema formation after amputation but failed to self-renew, leading to tissue regression and lysis.
• Neoblasts lacking Bruli could respond to stimuli and produce differentiated progeny but could not self-renew.

Conclusions:

• Bruno-like (bruli) is essential for the self-renewal and maintenance of planarian stem cells (neoblasts).
• bruli acts as a critical regulator for sustaining the pluripotent stem cell pool required for regeneration.