---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '21752'
abstract:
- lang: eng
  text: 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.
acknowledgement: This work was supported by JSPS/MEXT KAKENHI (grant numbers JP22J01430
  to H.N., JP23H04696, JP23K24025, JP25H02543, JP25K02406 to Y.N.), JST FOREST Program
  JPMJFR233E (Y.N.), The Cell Science Research Foundation (Y.N.), and Takeda Science
  Foundation (Y.N.).
article_number: '103670'
article_processing_charge: Yes (in subscription journal)
article_type: review
author:
- first_name: Hiroki
  full_name: Nagai, Hiroki
  id: 608df3e6-e2ab-11ed-8890-c9318cec7da4
  last_name: Nagai
  orcid: 0000-0003-1671-9434
- first_name: Yu Ichiro
  full_name: Nakajima, Yu Ichiro
  last_name: Nakajima
citation:
  ama: 'NAGAI H, Nakajima YI. Epithelial cell plasticity in metazoans: Evolutionary
    insights into roles and mechanisms. <i>Seminars in Cell and Developmental Biology</i>.
    2026;179-180. doi:<a href="https://doi.org/10.1016/j.semcdb.2026.103670">10.1016/j.semcdb.2026.103670</a>'
  apa: 'NAGAI, H., &#38; Nakajima, Y. I. (2026). Epithelial cell plasticity in metazoans:
    Evolutionary insights into roles and mechanisms. <i>Seminars in Cell and Developmental
    Biology</i>. Elsevier. <a href="https://doi.org/10.1016/j.semcdb.2026.103670">https://doi.org/10.1016/j.semcdb.2026.103670</a>'
  chicago: 'NAGAI, HIROKI, and Yu Ichiro Nakajima. “Epithelial Cell Plasticity in
    Metazoans: Evolutionary Insights into Roles and Mechanisms.” <i>Seminars in Cell
    and Developmental Biology</i>. Elsevier, 2026. <a href="https://doi.org/10.1016/j.semcdb.2026.103670">https://doi.org/10.1016/j.semcdb.2026.103670</a>.'
  ieee: 'H. NAGAI and Y. I. Nakajima, “Epithelial cell plasticity in metazoans: Evolutionary
    insights into roles and mechanisms,” <i>Seminars in Cell and Developmental Biology</i>,
    vol. 179–180. Elsevier, 2026.'
  ista: 'NAGAI H, Nakajima YI. 2026. Epithelial cell plasticity in metazoans: Evolutionary
    insights into roles and mechanisms. Seminars in Cell and Developmental Biology.
    179–180, 103670.'
  mla: 'NAGAI, HIROKI, and Yu Ichiro Nakajima. “Epithelial Cell Plasticity in Metazoans:
    Evolutionary Insights into Roles and Mechanisms.” <i>Seminars in Cell and Developmental
    Biology</i>, vol. 179–180, 103670, Elsevier, 2026, doi:<a href="https://doi.org/10.1016/j.semcdb.2026.103670">10.1016/j.semcdb.2026.103670</a>.'
  short: H. NAGAI, Y.I. Nakajima, Seminars in Cell and Developmental Biology 179–180
    (2026).
corr_author: '1'
date_created: 2026-04-19T22:07:49Z
date_published: 2026-05-01T00:00:00Z
date_updated: 2026-04-28T14:11:13Z
day: '01'
ddc:
- '570'
department:
- _id: XiFe
doi: 10.1016/j.semcdb.2026.103670
file:
- access_level: open_access
  checksum: 0a0929a045d0cbd964297768833c14ae
  content_type: application/pdf
  creator: dernst
  date_created: 2026-04-28T13:58:47Z
  date_updated: 2026-04-28T13:58:47Z
  file_id: '21775'
  file_name: 2026_SeminarsCellDevBiology_Nagai.pdf
  file_size: 1306613
  relation: main_file
  success: 1
file_date_updated: 2026-04-28T13:58:47Z
has_accepted_license: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
publication: Seminars in Cell and Developmental Biology
publication_identifier:
  eissn:
  - 1096-3634
  issn:
  - 1084-9521
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Epithelial cell plasticity in metazoans: Evolutionary insights into roles
  and mechanisms'
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 179-180
year: '2026'
...