Finding of STEMIN (STEM CELL INDUCING FACTOR) for feasible reprogramming in plants

Stem cells self-renew and give rise to cells that are differentiated during development. These differentiated cells can change into stem cells under appropriate conditions in most plants, in which this process is more readily apparent, and some animals. Researchers have previously succeeded in forming new shoots from intact leaves by inducing single transcription factors in Arabidopsis. However, it has not been clear whether these transcription factors induce meristematic tissue that subsequently induces stem cells or directly induces them. To this end, Assistant Professor Masaki Ishikawa and Professor Mitsuyasu Hasebe at the National Institute of Basic Biology in Japan, Designated Associate Professor Yoshikatsu Sato of the Institute of Transformative Bio-Molecules (WPI-ITbM) at Nagoya University in Japan and their collaborators found that induction of the transcription factor STEM CELL INDUCING FACTOR1 (STEMIN1) in leaves directly changes leaf cells into stem cells in the moss Physcomitrella patens. This discovery of a direct stem cell inducing factor will facilitate the further elucidation of the molecular mechanisms underlying stem cell formation in land plants.

In most plants and some animals, differentiated cells can revert to stem cells during or even after development under appropriate conditions. While stem cells do not appear to initiate after embryogenesis in mammalians, induction of some transcription factors induces conversion of somatic cells to induced pluripotent stem (iPS) cells. However, plant cells are more plastic than animal cells. In particular, stem cell formation is widely observed in the process of making new organs during development and regeneration in land plants. However, Professor Mitsuyasu Hasebe said, “Although some regulators involved in stem cell formation have been identified in angiosperms, understanding the molecular mechanisms of reprogramming and stem cell formation in land plants in general as well as their evolution is still challenging.”

Prof. Hasebe and his colleagues aimed to understand molecular mechanisms underlying stem cell formation by using the moss Physcomitrella patens and started a research project named “ERATO Hasebe Reprogramming Evolution project” supported by the Japan Science and Technology Agency in 2005. This moss is a good model to study stem cell formation from differentiated cells. The leafy shoot (gametophore) is formed after a hypha-like branching growth of a filamentous tissue (protonema) has arisen from a spore. When a leaf is excised from a gametophore and cultivated on a culture medium, leaf cells facing the cut convert into stem cells that can undergo tip growth and cell division to produce protonema. In screening for factors involved in stem cell formation, Dr. Yohei Higuchi and Dr. Yoshikatsu Sato, a group leader of the project, succeeded in identifying a gene encoding a transcription factor that changes leaf cells into stem cells without wounding signals, thus leading to formation of protonemata. Dr. Sato said, “This gene was named STEMIN1 (STEM CELL-INDUCING FACTOR 1)”.

After the project, Dr. Masaki Ishikawa succeeded in revealing the molecular mechanisms of STEMIN1 during stem cell formation. He said, “We found that STEMIN1 gene was activated in leaf cells that underwent stem cell formation in excised leaves. Furthermore, the deletion of STEMIN1 and its two homolog genes delayed the stem cell formation after leaf excision. These results indicate that STEMIN1 functions in an inherent mechanism to initiate formation of stem cells in Physcomitrella.” To further understand this molecular mechanism, Ms. Mio Morishita, a graduate student from SOKENDAI (The Graduate University for Advanced Studies) focused on the STEMIN1-direct target genes. She found that the genes were marked by trimethylation of histone H3 at lysine-27 (H3K27me3), a so-called repressive histone modification, and were transcriptionally repressed in leaf cells. In contrast to this, she also said, “STEMIN1 induction in leaf cells specifically decreased the repressive histone modification levels in the STEMIN1-direct target genes before cell division and activated their gene expression, leading to the formation of stem cells.”

Thus, this research group has demonstrated that STEMIN1 functions in an intrinsic mechanism underlying local histone modification changes to initiate stem cell formation. Prof. Hasebe said, “Our new findings will enhance studies on mechanistic insights regarding how a single transcription factor induces stem cell formation in land plants. In addition, since other land plants including angiosperms have orthologs of the STEMIN genes, further studies of this gene family should provide insight into whether this is a general mechanism for stem cell formation in land plants.”

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The above studies were published in Nature Plants on July 8th, 2019.

Nature Plants

“Physcomitrella STEMIN transcription factor induces stem cell formation with epigenetic reprogramming” by *Masaki Ishikawa, *Mio Morishita, Yohei Higuchi, Shunsuke Ichikawa, Takaaki Ishikawa, Tomoaki Nishiyama, Yukiko Kabeya, Yuji Hiwatashi, Tetsuya Kurata, Minoru Kubo, Shuji Shigenobu, Yosuke Tamada, Yoshikatsu Sato, and Mitsuyasu Hasebe (*Co-first authors)

DOI: 10.1038/s41477-019-0464-2 (https://doi.org/10.1038/s41477-019-0464-2)