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Peer-reviewedCC BYAdvanced science (Weinheim, Baden-Wurttemberg, Germany)

Acinar-Derived Organoids Reveal Stage-Specific Control of Acinar Plasticity.

  • Yongfei Hou1
  • Siyu Li1
  • Chunying Li1
  • Zhifan Lin1
  • Dan He1,2
  • Li Yang1
  • Liping Fu1
  • Qianyue Zhang1
  • Tianping Zhou3
  • Yao Yao1
  • Xiaolei Yin1
  1. 1Institute for Regenerative Medicine, State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  2. 2Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
  3. 3Department of Orthopedics, Zhabei Central Hospital Affiliated to Tongji University, Shanghai, China.
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Abstract

Adult pancreatic acinar cells undergo ordered metaplastic conversion during injury and tumor initiation. Whether individual cells retain redifferentiation capacity after metaplastic expansion, and what signals each transition requires, remains unknown. Here, using organoids derived from single acinar cells, we show that expanded acinar-lineage organoids can reacquire acinar features under stage-specific culture conditions. We defined conditions that preserve acinar identity ex vivo and showed that epidermal growth factor (EGF)/EGF receptor (EGFR) signaling initiates conversion from this maintained state. The expansion trajectory recapitulates injury- and oncogene-associated acinar-to-ductal metaplasia (ADM) programs in vivo. After expansion, the conditions that preserved acinar identity could not restore it; a staged regimen containing transient insulin-like growth factor 1 receptor (IGF1R) inhibition and dexamethasone promoted redifferentiation. The KrasG12D;Trp53R172H;Pdx1-Cre (KPC) genotype reduced EGFR dependence during initiation but destabilized post-expansion redifferentiation; Kras-pathway inhibition increased endpoint acinar-marker expression. These findings demonstrate that acinar plasticity is organized by stage-specific signals, and that the KPC genotype disrupts this control at specific transition points.

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Cite

BibTeXRIS
BibTeX
@article{hou2026acinarderived,
  title = {{Acinar-Derived Organoids Reveal Stage-Specific Control of Acinar Plasticity.}},
  author = {Yongfei Hou and Siyu Li and Chunying Li and Zhifan Lin and Dan He and Li Yang and Liping Fu and Qianyue Zhang and Tianping Zhou and Yao Yao and Xiaolei Yin},
  journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.78350},
  url = {https://europepmc.org/article/MED/42893502},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Acinar-Derived Organoids Reveal Stage-Specific Control of Acinar Plasticity.
AU  - Yongfei Hou
AU  - Siyu Li
AU  - Chunying Li
AU  - Zhifan Lin
AU  - Dan He
AU  - Li Yang
AU  - Liping Fu
AU  - Qianyue Zhang
AU  - Tianping Zhou
AU  - Yao Yao
AU  - Xiaolei Yin
PY  - 2026
DA  - 2026/10/18
JO  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO  - 10.1002/advs.78350
UR  - https://europepmc.org/article/MED/42893502
AB  - Adult pancreatic acinar cells undergo ordered metaplastic conversion during injury and tumor initiation. Whether individual cells retain redifferentiation capacity after metaplastic expansion, and what signals each transition requires, remains unknown. Here, using organoids derived from single acinar cells, we show that expanded acinar-lineage organoids can reacquire acinar features under stage-specific culture conditions. We defined conditions that preserve acinar identity ex vivo and showed that epidermal growth factor (EGF)/EGF receptor (EGFR) signaling initiates conversion from this maintained state. The expansion trajectory recapitulates injury- and oncogene-associated acinar-to-ductal metaplasia (ADM) programs in vivo. After expansion, the conditions that preserved acinar identity could not restore it; a staged regimen containing transient insulin-like growth factor 1 receptor (IGF1R) inhibition and dexamethasone promoted redifferentiation. The KrasG12D;Trp53R172H;Pdx1-Cre (KPC) genotype reduced EGFR dependence during initiation but destabilized post-expansion redifferentiation; Kras-pathway inhibition increased endpoint acinar-marker expression. These findings demonstrate that acinar plasticity is organized by stage-specific signals, and that the KPC genotype disrupts this control at specific transition points.
SN  - 2198-3844
ER  -