Unraveling the role of Djstat5 in planarian regeneration by modulating cell proliferation and apoptosis

Freshwater planarians can regrow entire bodies from tiny fragments within days. This “immortality” relies on adult pluripotent stem cells (neoblasts), which act as the key mediators. Yet, how do injury signals activate these stem cells and initiate tissue reconstruction?

Recently, a team led by Prof. Fu‑Lin Chen and Assoc. Prof. Yuan Yu from Northwest University published a study in Zoological Research, revealing for the first time that the transcription factor Djstat5 acts as a critical “molecular switch.” By suppressing the negative regulator Djnlrc3, Djstat5 precisely coordinates the balance between cell proliferation and apoptosis, thereby driving perfect tissue reconstruction.

Key Trigger for Regeneration: Djstat5 Is Rapidly Upregulated Upon Injury

The team first cloned the Djstat5 gene from the planarian Dugesia japonica. Expression analysis showed that Djstat5 is not only expressed in planarian adult pluripotent stem cells but also significantly upregulated during early regeneration after injury, with enrichment in the blastema region—suggesting its role in early regeneration.

Knockdown of Djstat5 Severely Impedes Planarian Regeneration

To further investigate Djstat5 function, the researchers used RNA interference to reduce its expression. Djstat5 deficiency severely blocked regeneration: blastema development was impaired, and organs such as eyes, brain, and intestine failed to regenerate. At the cellular level, stem cell division activity dropped sharply, and normal apoptosis also decreased. These findings indicate that Djstat5 is essential for coordinating proliferation and apoptosis during regeneration, ensuring effective tissue repair.

Transcriptome Analysis Identifies Potential Regulator Djnlrc3

To dissect the molecular mechanism, the team performed transcriptome sequencing of blastema tissue, identifying 350 differentially expressed genes. Among them, abnormal elevation of Djnlrc3 drew attention—NLRC3 is a known negative regulator of PI3K-AKT signaling in mammals, inhibiting cell proliferation. The researchers hypothesized that Djstat5 deficiency caused aberrant Djnlrc3 activation, which weakened pro-regenerative signals. Further experiments confirmed that Djstat5 loss reduced PI3K-AKT activity.

Double RNAi Reveals the Djstat5-Djnlrc3 Regulatory Axis

To verify whether Djnlrc3 mediates these defects, double RNAi of Djstat5 and Djnlrc3 was performed. Simultaneous knockdown partially restored regeneration—blastema re-formed, and defects in the brain, intestine, and pharynx were rescued to varying degrees, with proliferation and apoptosis rebounding. This confirms the Djstat5-Djnlrc3 axis as central to planarian regeneration.

In summary, this study elucidates that the Djstat5-Djnlrc3 axis drives planarian adult stem cell mediated tissue regeneration by coordinating proliferation and apoptosis. This provides new evidence for the evolutionary conservation of regenerative signaling pathways and opens new perspectives on adult stem cell repair mechanisms.
This study was published in Zoological Research under the title “Unraveling the role of Djstat5 in planarian regeneration by modulating cell proliferation and apoptosis.” For more details, please visit the article link.

Title:

Unraveling the role of Djstat5 in planarian regeneration by modulating cell proliferation and apoptosis

Journal Name: Zoological Research

DOI: 10.24272/j.issn.2095-8137.2025.356

URL:https://scholarcast.cast.org.cn/top-news/2080545223703396352