IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41418-z.html
   My bibliography  Save this article

A CCL2+DPP4+ subset of mesenchymal stem cells expedites aberrant formation of creeping fat in humans

Author

Listed:
  • Fengfei Wu

    (Southern Medical University)

  • Fangting Wu

    (Southern Medical University)

  • Qian Zhou

    (Southern Medical University)

  • Xi Liu

    (Southern Medical University)

  • Jieying Fei

    (Southern Medical University)

  • Da Zhang

    (Southern Medical University)

  • Weidong Wang

    (Southern Medical University)

  • Yi Tao

    (Southern Medical University)

  • Yubing Lin

    (Southern Medical University)

  • Qiaoqiao Lin

    (Southern Medical University)

  • Xinghua Pan

    (Southern Medical University, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application)

  • Kai Sun

    (Southern Medical University)

  • Fang Xie

    (Southern Medical University)

  • Lan Bai

    (Southern Medical University)

Abstract

Creeping fat is a typical feature of Crohn’s disease. It refers to the expansion of mesenteric adipose tissue around inflamed and fibrotic intestines and is associated with stricture formation and intestinal obstruction. In this study, we characterize creeping fat as pro-adipogenic and pro-fibrotic. Lipidomics analysis of Crohn’s disease patients (sixteen males, six females) and healthy controls (five males, ten females) reveals abnormal lipid metabolism in creeping fat. Through scRNA-seq analysis on mesenteric adipose tissue from patients (five males, one female) and healthy controls (two females), we identify a CCL2+DPP4+ subset of mesenchymal stem cells that expands in creeping fat and expedites adipogenic differentiation into dystrophic adipocytes in response to CCL20+CD14+ monocytes and IL-6, leading to the formation of creeping fat. Ex vivo experiments (tissues from five males, one female) confirm that both CCL20+CD14+ monocytes and IL-6 activate DPP4+ mesenchymal stem cells towards a pro-adipogenic phenotype. This study provides a comprehensive investigation of creeping fat formation and offers a conceptual framework for discovering therapeutic targets for treatment of Crohn’s disease.

Suggested Citation

  • Fengfei Wu & Fangting Wu & Qian Zhou & Xi Liu & Jieying Fei & Da Zhang & Weidong Wang & Yi Tao & Yubing Lin & Qiaoqiao Lin & Xinghua Pan & Kai Sun & Fang Xie & Lan Bai, 2023. "A CCL2+DPP4+ subset of mesenchymal stem cells expedites aberrant formation of creeping fat in humans," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41418-z
    DOI: 10.1038/s41467-023-41418-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41418-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41418-z?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. Shikha Nayar & Joshua K. Morrison & Mamta Giri & Kyle Gettler & Ling-shiang Chuang & Laura A. Walker & Huaibin M. Ko & Ephraim Kenigsberg & Subra Kugathasan & Miriam Merad & Jaime Chu & Judy H. Cho, 2021. "A myeloid–stromal niche and gp130 rescue in NOD2-driven Crohn’s disease," Nature, Nature, vol. 593(7858), pages 275-281, May.
    2. Petra C. Schwalie & Hua Dong & Magda Zachara & Julie Russeil & Daniel Alpern & Nassila Akchiche & Christian Caprara & Wenfei Sun & Kai-Uwe Schlaudraff & Gianni Soldati & Christian Wolfrum & Bart Depla, 2018. "A stromal cell population that inhibits adipogenesis in mammalian fat depots," Nature, Nature, vol. 559(7712), pages 103-108, July.
    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. Riley D. Metcalfe & Eric Hanssen & Ka Yee Fung & Kaheina Aizel & Clara C. Kosasih & Courtney O. Zlatic & Larissa Doughty & Craig J. Morton & Andrew P. Leis & Michael W. Parker & Paul R. Gooley & Tracy, 2023. "Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Lucas Massier & Jutta Jalkanen & Merve Elmastas & Jiawei Zhong & Tongtong Wang & Pamela A. Nono Nankam & Scott Frendo-Cumbo & Jesper Bäckdahl & Narmadha Subramanian & Takuya Sekine & Alastair G. Kerr , 2023. "An integrated single cell and spatial transcriptomic map of human white adipose tissue," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Shengnan Liu & Siyi Shen & Ying Yan & Chao Sun & Zhiqiang Lu & Hua Feng & Yiruo Ma & Zhili Tang & Jing Yu & Yuting Wu & Balázs Gereben & Petra Mohácsik & Csaba Fekete & Xiaoyun Feng & Feixiang Yuan & , 2022. "Triiodothyronine (T3) promotes brown fat hyperplasia via thyroid hormone receptor α mediated adipocyte progenitor cell proliferation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Egle Kvedaraite & Magda Lourda & Natalia Mouratidou & Tim Düking & Avinash Padhi & Kirsten Moll & Paulo Czarnewski & Indranil Sinha & Ioanna Xagoraris & Efthymia Kokkinou & Anastasios Damdimopoulos & , 2024. "Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Jie Gao & Lei Wang & Jing Jiang & Qian Xu & Nianyi Zeng & Bingyun Lu & Peibo Yuan & Kai Sun & Hongwei Zhou & Xiaolong He, 2023. "A probiotic bi-functional peptidoglycan hydrolase sheds NOD2 ligands to regulate gut homeostasis in female mice," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Matthew C. Sinton & Praveena R. G. Chandrasegaran & Paul Capewell & Anneli Cooper & Alex Girard & John Ogunsola & Georgia Perona-Wright & Dieudonné M Ngoyi & Nono Kuispond & Bruno Bucheton & Mamadou C, 2023. "IL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    7. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, 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:14:y:2023:i:1:d:10.1038_s41467-023-41418-z. 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.