@article{21039,
  abstract     = {Cellular plasticity, the ability of a differentiated cell to adopt another phenotypic identity, is restricted under basal conditions, but can be elicited upon damage. However, the molecular mechanism enabling such plasticity remains largely unexplored. Here, we report damage-induced cellular plasticity of secretory enteroendocrine cells (EEs) in the adult Drosophila midgut. Ionizing radiation induces EE fate conversion and activates stress-responsive programs in EE lineages, accompanied by the induction of the stress-inducible transcription factor Xrp1 and the cytokine gene upd3. Xrp1 and upd3 are both necessary for radiation-induced EE plasticity. Under basal conditions, EE-specific Xrp1 overexpression triggers ectopic expression of progenitor-specific genes, which is necessary for Xrp1 to drive EE plasticity. Our work identifies Xrp1 as a crucial regulator that coordinates damage-induced signaling and transcriptional reprogramming, enabling the reactivation of cellular plasticity in differentiated cells.},
  author       = {Qian, Qingyin and Nagai, Hiroki and Sanaki, Yuya and Hayashi, Makoto and Kimura, Kenichi and Nakajima, Yu Ichiro and Niwa, Ryusuke},
  issn         = {1477-9129},
  journal      = {Development},
  number       = {2},
  publisher    = {The Company of Biologists},
  title        = {{Xrp1 drives damage-induced cellular plasticity of enteroendocrine cells in the adult Drosophila midgut}},
  doi          = {10.1242/dev.205225},
  volume       = {153},
  year         = {2026},
}

@article{21752,
  abstract     = {Epithelial tissues function as multicellular communities that preserve tissue integrity while adapting to diverse environmental stresses by altering cell behaviors. A striking manifestation of such adaptability is cell plasticity, the ability of differentiated cells to revert to stem-like states or adopt alternative fates. Once considered rare and confined to highly regenerative species, cell plasticity is now recognized across the metazoan tree. In early-branching animals such as sponges and cnidarians, transdifferentiation and dedifferentiation are integral to life-cycle transitions and regeneration, whereas in more complex organisms, these processes typically emerge under stress, including stem cell loss or environmental perturbations. Here, we examine epithelial cell plasticity through evolutionary, cellular, and molecular perspectives. Focusing on the intestinal epithelium, we explore findings from mammalian and Drosophila models showing that progenitors and even terminally differentiated cells can dedifferentiate in response to external stimuli that disrupt homeostasis, such as pathogen infection and nutrient fluctuations. We further discuss conserved mechanisms involving intercellular signaling (e.g., Notch, EGFR, and JAK-STAT) and chromatin states primed for reprogramming, modulated by metabolic cues. Together, these insights position cell plasticity as an ancient environmental adaptation strategy, shaped by conserved molecular toolkits and refined by species- and cell lineage-specific innovations.},
  author       = {Nagai, Hiroki and Nakajima, Yu Ichiro},
  issn         = {1096-3634},
  journal      = {Seminars in Cell and Developmental Biology},
  publisher    = {Elsevier},
  title        = {{Epithelial cell plasticity in metazoans: Evolutionary insights into roles and mechanisms}},
  doi          = {10.1016/j.semcdb.2026.103670},
  volume       = {179-180},
  year         = {2026},
}

@article{21716,
  abstract     = {Male germline development in plants is highly sensitive to heat stress, with elevated temperatures frequently impairing male fertility and consequently reducing seed production. Indeed, recent global warming has decreased major crop yields, emphasizing the urgent need to elucidate the molecular and cellular mechanisms underlying heat-induced male sterility. This review synthesizes current knowledge on how heat stress disrupts microsporogenesis and microgametogenesis, and how plants counteract these stresses through diverse thermotolerance mechanisms. We emphasize temperature-sensitive processes, including meiotic progression in male germ cells, programmed cell death of somatic tapetal nurse cells, and post-meiotic pollen tube development. We further discuss how epigenetic regulators enhance thermotolerance by reprogramming DNA methylation landscapes and modulating histone variant distribution. Finally, we propose future directions aimed at understanding the mechanisms of reproductive thermotolerance from the epigenetic perspective.},
  author       = {Nagai, Hiroki and Feng, Xiaoqi},
  issn         = {1879-0356},
  journal      = {Current Opinion in Plant Biology},
  number       = {6},
  publisher    = {Elsevier},
  title        = {{Genetic and epigenetic mechanisms underlying male reproductive thermotolerance}},
  doi          = {10.1016/j.pbi.2026.102881},
  volume       = {91},
  year         = {2026},
}

@article{17408,
  abstract     = {Background: The remarkable regenerative abilities observed in planarians and cnidarians are closely linked to the active proliferation of adult stem cells and the precise differentiation of their progeny, both of which typically deteriorate during aging in low regenerative animals. While regeneration-specific genes conserved in highly regenerative organisms may confer regenerative abilities and long-term maintenance of tissue homeostasis, it remains unclear whether introducing these regenerative genes into low regenerative animals can improve their regeneration and aging processes.

Results: Here, we ectopically express highly regenerative species-specific JmjC domain-encoding genes (HRJDs) in Drosophila, a widely used low regenerative model organism. Surprisingly, HRJD expression impedes tissue regeneration in the developing wing disc but extends organismal lifespan when expressed in the intestinal stem cell lineages of the adult midgut under non-regenerative conditions. Notably, HRJDs enhance the proliferative activity of intestinal stem cells while maintaining their differentiation fidelity, ameliorating age-related decline in gut barrier functions.

Conclusions: These findings together suggest that the introduction of highly regenerative species-specific genes can improve stem cell functions and promote a healthy lifespan when expressed in aging animals.},
  author       = {Nagai, Hiroki and Adachi, Yuya and Nakasugi, Tenki and Takigawa, Ema and Ui, Junichiro and Makino, Takashi and Miura, Masayuki and Nakajima, Yu Ichiro},
  issn         = {1741-7007},
  journal      = {BMC Biology},
  publisher    = {Springer Nature},
  title        = {{Highly regenerative species-specific genes improve age-associated features in the adult Drosophila midgut}},
  doi          = {10.1186/s12915-024-01956-4},
  volume       = {22},
  year         = {2024},
}