Zoological Society of Japan, Hokkaido Branch, 603rd Branch Lecture

Date and Time: Friday, February 7, 2025, from 5:00 PM to 6:30 PM
Location: Hokkaido University, Faculty of Science Building No. 5, 4th Floor, Room 407

Speaker: Dr. Shinji Yamaguchi (Professor, Faculty of Pharmaceutical Sciences, Teikyo University)

Title: Discovery of Cells Promoting Regeneration ~Usefulness of Enchytraeus japonensis as a Regeneration Model~

Abstract: Humans cannot regenerate organs lost to injury. On the other hand, there are animals with high regenerative capacity that can regenerate their entire bodies from small fragments (whole-body regeneration). Many aspects of "what cellular and molecular bases account for the differences in regenerative capacity among biological species?" remain unclear.
The annelid earthworm *Enchytraeus japonensis* has the capacity for whole-body regeneration. During regeneration, it forms a "blastema"—a mass of undifferentiated cells—at the cut end, which serves as the material to rebuild lost organs. Through comparative RNA-seq analysis, the speaker identified *soxC* as the transcription factor whose expression increases the most during blastema formation. When *soxC* expression was suppressed using RNA interference newly established in *Enchytraeus japonensis*, the blastema became smaller, indicating that *soxC* is required for blastema formation. Next, expression analysis associated with blastema formation revealed that *soxC*-expressing cells gradually accumulate in the blastema and eventually occupy almost the entire blastema. Based on these findings, the speaker proposed the concept that *soxC*-expressing cells are "blastema progenitor cells" that migrate to the blastema (Nat. Commun. [2024]). Furthermore, using *Xenopus laevis* larvae (tadpoles), which are vertebrates with high regenerative capacity, the expression of *soxC* orthologs was examined in the blastema formed at the cut end of the tail. Surprisingly, it was shown that *soxC*-expressing cells also accumulate in the tadpole blastema. Although it was previously thought that the mechanisms of blastema formation in invertebrates (earthworms) and vertebrates (frogs) were completely different, the common accumulation of *soxC*-expressing cells suggests that organ regeneration may occur through mechanisms common across animal species. Given that *soxC* exists even in humans—who, with the exception of the liver, lack organs with high regenerative capacity—clarifying the cellular dynamics of *soxC*-expressing cells (= blastema progenitor cells) is expected to provide new perspectives for novel drug discovery and regenerative medicine.

The 603rd Annual Meeting of the Zoological Society of Japan, Hokkaido Branch