IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49724-w.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49724-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-49724-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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. 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.
    3. 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.
    4. 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.
    5. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yuqian Wang & Renqi Huang & Yougong Lu & Mingqi Liu & Ran Mo, 2024. "Immuno-protective vesicle-crosslinked hydrogel for allogenic transplantation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Pietro Demela & Nicola Pirastu & Blagoje Soskic, 2023. "Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Paul M. H. Tran & Fran Dong & Eileen Kim & Katherine P. Richardson & Lynn K. H. Tran & Kathleen Waugh & Diane Hopkins & Richard D. Cummings & Peng George Wang & Marian J. Rewers & Jin-Xiong She & Shar, 2022. "Use of a glycomics array to establish the anti-carbohydrate antibody repertoire in type 1 diabetes," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Xiaojie Ma & Jie Cao & Ziyu Zhou & Yunkun Lu & Qin Li & Yan Jin & Guo Chen & Weiyun Wang & Wenyan Ge & Xi Chen & Zhensheng Hu & Xiao Shu & Qian Deng & Jiaqi Pu & Chengzhen Liang & Junfen Fu & Jianzhao, 2022. "N6-methyladenosine modification-mediated mRNA metabolism is essential for human pancreatic lineage specification and islet organogenesis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Chachrit Khunsriraksakul & Qinmengge Li & Havell Markus & Matthew T. Patrick & Renan Sauteraud & Daniel McGuire & Xingyan Wang & Chen Wang & Lida Wang & Siyuan Chen & Ganesh Shenoy & Bingshan Li & Xue, 2023. "Multi-ancestry and multi-trait genome-wide association meta-analyses inform clinical risk prediction for systemic lupus erythematosus," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Parker C. Wilson & Yoshiharu Muto & Haojia Wu & Anil Karihaloo & Sushrut S. Waikar & Benjamin D. Humphreys, 2022. "Multimodal single cell sequencing implicates chromatin accessibility and genetic background in diabetic kidney disease progression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    7. Jennifer P. Nguyen & Timothy D. Arthur & Kyohei Fujita & Bianca M. Salgado & Margaret K. R. Donovan & Hiroko Matsui & Ji Hyun Kim & Agnieszka D’Antonio-Chronowska & Matteo D’Antonio & Kelly A. Frazer, 2023. "eQTL mapping in fetal-like pancreatic progenitor cells reveals early developmental insights into diabetes risk," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    8. Clara Albiñana & Zhihong Zhu & Nis Borbye-Lorenzen & Sanne Grundvad Boelt & Arieh S. Cohen & Kristin Skogstrand & Naomi R. Wray & Joana A. Revez & Florian Privé & Liselotte V. Petersen & Cynthia M. Bu, 2023. "Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Guanlan Xu & Tiffany D. Grimes & Truman B. Grayson & Junqin Chen & Lance A. Thielen & Hubert M. Tse & Peng Li & Matt Kanke & Tai-Tu Lin & Athena A. Schepmoes & Adam C. Swensen & Vladislav A. Petyuk & , 2022. "Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    10. Matthew T. Patrick & Qinmengge Li & Rachael Wasikowski & Nehal Mehta & Johann E. Gudjonsson & James T. Elder & Xiang Zhou & Lam C. Tsoi, 2022. "Shared genetic risk factors and causal association between psoriasis and coronary artery disease," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    11. Chun Jing Wang & Lina Petersone & Natalie M. Edner & Frank Heuts & Vitalijs Ovcinnikovs & Elisavet Ntavli & Alexandros Kogimtzis & Astrid Fabri & Yassin Elfaki & Luke P. Houghton & Ralf J. Hosse & Dav, 2022. "Costimulation blockade in combination with IL-2 permits regulatory T cell sparing immunomodulation that inhibits autoimmunity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    12. Shenqiang Wang & Ying Zhang & Yanfang Wang & Yinxian Yang & Sheng Zhao & Tao Sheng & Yuqi Zhang & Zhen Gu & Jinqiang Wang & Jicheng Yu, 2023. "An in situ dual-anchoring strategy for enhanced immobilization of PD-L1 to treat autoimmune diseases," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    13. Keiichi Katsumoto & Siham Yennek & Chunguang Chen & Luis Fernando Delgadillo Silva & Sofia Traikov & Dror Sever & Ajuna Azad & Jingdong Shan & Seppo Vainio & Nikolay Ninov & Stephan Speier & Anne Grap, 2022. "Wnt4 is heterogeneously activated in maturing β-cells to control calcium signaling, metabolism and function," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Romana Bohuslavova & Valeria Fabriciova & Ondrej Smolik & Laura Lebrón-Mora & Pavel Abaffy & Sarka Benesova & Daniel Zucha & Lukas Valihrach & Zuzana Berkova & Frantisek Saudek & Gabriela Pavlinkova, 2023. "NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    15. Zhuo Ma & Xiaofei Zhang & Wen Zhong & Hongyan Yi & Xiaowei Chen & Yinsuo Zhao & Yanlin Ma & Eli Song & Tao Xu, 2023. "Deciphering early human pancreas development at the single-cell level," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49724-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.