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Physcomitrella STEMIN transcription factor induces stem cell formation with epigenetic reprogramming


Epigenetic modifications, including histone modifications, stabilize cell-specific gene expression programmes to maintain cell identities in both metazoans and land plants1,2,3. Notwithstanding the existence of these stable cell states, in land plants, stem cells are formed from differentiated cells during post-embryonic development and regeneration4,5,6, indicating that land plants have an intrinsic ability to regulate epigenetic memory to initiate a new gene regulatory network. However, it is less well understood how epigenetic modifications are locally regulated to influence the specific genes necessary for cellular changes without affecting other genes in a genome. In this study, we found that ectopic induction of the AP2/ERF transcription factor STEMIN1 in leaf cells of the moss Physcomitrella patens decreases a repressive chromatin mark, histone H3 lysine 27 trimethylation (H3K27me3), on its direct target genes before cell division, resulting in the conversion of leaf cells to chloronema apical stem cells. STEMIN1 and its homologues positively regulate the formation of secondary chloronema apical stem cells from chloronema cells during development. Our results suggest that STEMIN1 functions within an intrinsic mechanism underlying local H3K27me3 reprogramming to initiate stem cell formation.

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Data availability

Sequence data for genes and plasmids discussed in this article can be found in DDBJ/GenBank/EMBL data libraries under the following accession numbers: STEMIN1 (Pp3c1_27440: LC042086), STEMIN2 (Pp3c14_9940: LC042087), STEMIN3 (Pp3c10_7030: LC042088), pLGZ1 (AB602442), pGX6M (LC388570), pT2GX6 (LC388571), pPIG1bNGGII (AB537478), p35S-loxP-BSD (AB537973), p35S-loxP-Zeo (AB540628) and pTN182 (AB267706). The ChIP-seq and RNA-seq data for identification of STEMIN1-target genes and the ChIP-seq data for histone modifications are deposited in the DDBJ Sequence Read Archive (DRA) with accession numbers DRA007364 and DRA007365, respectively. The data that support the findings of this study are available from the corresponding authors upon request.

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Competing interests

The authors declare no competing interests.

Additional information

Peer review information: Nature Plants thanks Frederic Berger and John Bowman and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


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The authors would like to thank N.-H. Chua for providing the pER8 vector; T. Murata and L. Zhang for time-lapse analysis; T. Aoyama for critical reading of the manuscript; K. Yamaguchi for next-generation sequencing; and K. Oba, E. Aoki, M. Goto, M. Kimura, M. Mawatari, T. Nishi, H. Okamoto, S. Ooi and N. Sugimoto for technical assistance. Moss cultivation and RNA-seq and ChIP-seq analyses were supported in part by the Model Plant Research Facility, the Functional Genomics Facility and the Data Integration and Analysis Facility of the National Institute for Basic Biology, Japan. This research was partly funded by JSPS KAKENHI grants (No. JP25291067 to M.I., T.N., Y.T. and M.H. and Nos. JP15K07119, JP18K06302 and JP18H04846 to M.I.) and by a JST ERATO programme grant to M.H.

Author information

M.I., M.M., Y. Higuchi, T.K., M.K., Y.S. and M.H. conceived and designed the research. Y. Higuchi and Y.S. identified STEMIN genes. M.I., M.M., Y. Higuchi, S.I. T.I. and S.S. performed the experiments. T.N. performed the phylogenetic analysis. Y.K. and Y. Hiwatashi performed transformation. M.M., T.N. and Y.T. analysed the RNA-seq and ChIP-seq data. M.I., M.M. and M.H. wrote the manuscript. All authors reviewed and edited the manuscript.

Competing interests

The authors declare no competing interests.

Correspondence to Masaki Ishikawa or Mitsuyasu Hasebe.

Supplementary information

Supplementary information

Supplementary Figs. 1–26, legends for Supplementary Tables 1,2 and Supplementary Videos 1–3, Supplementary Table 3, and Supplementary References.

Reporting Summary

Supplementary Table 1

Differentially expressed genes in the GX6:STEMIN1-Myc#11 line with or without β-oestradiol.

Supplementary Table 2

STEMIN1 direct target genes in the GX6:STEMIN1-Myc#11 line.

Supplementary Dataset 1

Alignment used to create the phylogenic tree of the STEMIN1 gene family in land plants in Supplementary Fig. 2.

Supplementary Video 1

The AP2/ERF transcription factor STEMIN1 induces stem cell formation.

Supplementary Video 2

STEMIN1 promoter activity in an excised leaf of a STEMIN1pro:NGG#7 plant.

Supplementary Video 3

STEMIN1 promoter activity in a chloronema cell of a STEMIN1pro:NGG#7 plant.

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Fig. 1: Stem cell induction by STEMIN1 expression.
Fig. 2: STEMIN has a positive function in stem cell formation in cut leaves.
Fig. 3: STEMIN1 induces reprogramming of protonema cells.
Fig. 4: Changes in histone modifications of STEMIN1 target genes.