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Identification of unique cell type responses in pancreatic islets to stress

Author

Listed:
  • Marlie M. Maestas

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Matthew Ishahak

    (Washington University School of Medicine)

  • Punn Augsornworawat

    (Mahidol University)

  • Daniel A. Veronese-Paniagua

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Kristina G. Maxwell

    (Washington University School of Medicine
    Washington University in St. Louis)

  • Leonardo Velazco-Cruz

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Erica Marquez

    (Washington University School of Medicine
    Washington University in St. Louis)

  • Jiameng Sun

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Mira Shunkarova

    (Washington University School of Medicine)

  • Sarah E. Gale

    (Washington University School of Medicine)

  • Fumihiko Urano

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Jeffrey R. Millman

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University in St. Louis)

Abstract

Diabetes involves the death or dysfunction of pancreatic β-cells. Analysis of bulk sequencing from human samples and studies using in vitro and in vivo models suggest that endoplasmic reticulum and inflammatory signaling play an important role in diabetes progression. To better characterize cell type-specific stress response, we perform multiplexed single-cell RNA sequencing to define the transcriptional signature of primary human islet cells exposed to endoplasmic reticulum and inflammatory stress. Through comprehensive pair-wise analysis of stress responses across pancreatic endocrine and exocrine cell types, we define changes in gene expression for each cell type under different diabetes-associated stressors. We find that β-, α-, and ductal cells have the greatest transcriptional response. We utilize stem cell-derived islets to study islet health through the candidate gene CIB1, which was upregulated under stress in primary human islets. Our findings provide insights into cell type-specific responses to diabetes-associated stress and establish a resource to identify targets for diabetes therapeutics.

Suggested Citation

  • Marlie M. Maestas & Matthew Ishahak & Punn Augsornworawat & Daniel A. Veronese-Paniagua & Kristina G. Maxwell & Leonardo Velazco-Cruz & Erica Marquez & Jiameng Sun & Mira Shunkarova & Sarah E. Gale & , 2024. "Identification of unique cell type responses in pancreatic islets to stress," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49724-w
    DOI: 10.1038/s41467-024-49724-w
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    References listed on IDEAS

    as
    1. Chien-Wen Chen & Bo-Jhih Guan & Mohammed R. Alzahrani & Zhaofeng Gao & Long Gao & Syrena Bracey & Jing Wu & Cheikh A. Mbow & Raul Jobava & Leena Haataja & Ajay H. Zalavadia & Ashleigh E. Schaffer & Hu, 2022. "Adaptation to chronic ER stress enforces pancreatic β-cell plasticity," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Joshua Chiou & Ryan J. Geusz & Mei-Lin Okino & Jee Yun Han & Michael Miller & Rebecca Melton & Elisha Beebe & Paola Benaglio & Serina Huang & Katha Korgaonkar & Sandra Heller & Alexander Kleger & Seba, 2021. "Interpreting type 1 diabetes risk with genetics and single-cell epigenomics," Nature, Nature, vol. 594(7863), pages 398-402, June.
    3. Jeffrey R. Millman & Chunhui Xie & Alana Van Dervort & Mads Gürtler & Felicia W. Pagliuca & Douglas A. Melton, 2016. "Generation of stem cell-derived β-cells from patients with type 1 diabetes," Nature Communications, Nature, vol. 7(1), pages 1-9, September.
    4. Maikel L. Colli & Mireia Ramos-Rodríguez & Ernesto S. Nakayasu & Maria I. Alvelos & Miguel Lopes & Jessica L. E. Hill & Jean-Valery Turatsinze & Alexandra Coomans de Brachène & Mark A. Russell & Helen, 2020. "An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    5. Eiji Yoshihara & Carolyn O’Connor & Emanuel Gasser & Zong Wei & Tae Gyu Oh & Tiffany W. Tseng & Dan Wang & Fritz Cayabyab & Yang Dai & Ruth T. Yu & Christopher Liddle & Annette R. Atkins & Michael Dow, 2020. "Immune-evasive human islet-like organoids ameliorate diabetes," Nature, Nature, vol. 586(7830), pages 606-611, October.
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