IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48914-w.html
   My bibliography  Save this article

Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis

Author

Listed:
  • Hongdong Wang

    (Drum Tower Hospital Affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases)

  • Yanhua Du

    (Shanghai Jiao Tong University School of Medicine)

  • Shanshan Huang

    (Drum Tower Hospital Affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases)

  • Xitai Sun

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Youqiong Ye

    (Shanghai Jiao Tong University School of Medicine)

  • Haixiang Sun

    (Drum Tower Hospital Affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases)

  • Xuehui Chu

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Xiaodong Shan

    (Drum Tower Hospital Affiliated to Nanjing University Medical School)

  • Yue Yuan

    (Drum Tower Hospital Affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases)

  • Lei Shen

    (Shanghai Jiao Tong University School of Medicine)

  • Yan Bi

    (Drum Tower Hospital Affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases)

Abstract

Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity and the role of APC subpopulations on regulating glucose homeostasis remain unknown. Here, we find that APCs in human visceral adipose tissue contain four subsets. The composition and functionality of APCs are altered in patients with type 2 diabetes (T2D). CD9+CD55low APCs are the subset which is significantly increased in T2D patients. Transplantation of these cells from T2D patients into adipose tissue causes glycemic disturbance. Mechanistically, CD9+CD55low APCs promote T2D development through producing bioactive proteins to form a detrimental niche, leading to upregulation of adipocyte lipolysis. Depletion of pathogenic APCs by inducing intracellular diphtheria toxin A expression or using a hunter-killer peptide improves obesity-related glycemic disturbance. Collectively, our data provide deeper insights in human APC functionality and highlights APCs as a potential therapeutic target to combat T2D. All mice utilized in this study are male.

Suggested Citation

  • Hongdong Wang & Yanhua Du & Shanshan Huang & Xitai Sun & Youqiong Ye & Haixiang Sun & Xuehui Chu & Xiaodong Shan & Yue Yuan & Lei Shen & Yan Bi, 2024. "Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48914-w
    DOI: 10.1038/s41467-024-48914-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48914-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-48914-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. Rona S. Scott & Eileen J. McMahon & Shannon M. Pop & Elizabeth A. Reap & Roberto Caricchio & Philip L. Cohen & H. Shelton Earp & Glenn K. Matsushima, 2001. "Phagocytosis and clearance of apoptotic cells is mediated by MER," Nature, Nature, vol. 411(6834), pages 207-211, May.
    2. Margo P. Emont & Christopher Jacobs & Adam L. Essene & Deepti Pant & Danielle Tenen & Georgia Colleluori & Angelica Vincenzo & Anja M. Jørgensen & Hesam Dashti & Adam Stefek & Elizabeth McGonagle & So, 2022. "A single-cell atlas of human and mouse white adipose tissue," Nature, Nature, vol. 603(7903), pages 926-933, March.
    3. Filipa Cardoso & Roel G. J. Klein Wolterink & Cristina Godinho-Silva & Rita G. Domingues & Hélder Ribeiro & Joaquim Alves da Silva & Inês Mahú & Ana I. Domingos & Henrique Veiga-Fernandes, 2021. "Neuro-mesenchymal units control ILC2 and obesity via a brain–adipose circuit," Nature, Nature, vol. 597(7876), pages 410-414, September.
    4. Hongdong Wang & Lei Shen & Xitai Sun & Fangcen Liu & Wenhuan Feng & Chunping Jiang & Xuehui Chu & Xiao Ye & Can Jiang & Yan Wang & Pengzi Zhang & Mengwei Zang & Dalong Zhu & Yan Bi, 2019. "Adipose group 1 innate lymphoid cells promote adipose tissue fibrosis and diabetes in obesity," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    5. 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.
    6. Junyue Cao & Malte Spielmann & Xiaojie Qiu & Xingfan Huang & Daniel M. Ibrahim & Andrew J. Hill & Fan Zhang & Stefan Mundlos & Lena Christiansen & Frank J. Steemers & Cole Trapnell & Jay Shendure, 2019. "The single-cell transcriptional landscape of mammalian organogenesis," Nature, Nature, vol. 566(7745), pages 496-502, February.
    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. Martin Uhrbom & Lars Muhl & Guillem Genové & Jianping Liu & Henrik Palmgren & Ida Alexandersson & Fredrik Karlsson & Alex-Xianghua Zhou & Sandra Lunnerdal & Sonja Gustafsson & Byambajav Buyandelger & , 2024. "Adipose stem cells are sexually dimorphic cells with dual roles as preadipocytes and resident fibroblasts," Nature Communications, Nature, vol. 15(1), pages 1-19, 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. Nadège Gruel & Chloé Quignot & Laëtitia Lesage & Sophie El Zein & Sylvie Bonvalot & Dimitri Tzanis & Khadija Ait Rais & Fabien Quinquis & Bastien Manciot & Julien Vibert & Nadine El Tannir & Ahmed Dah, 2024. "Cellular origin and clonal evolution of human dedifferentiated liposarcoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. 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.
    5. Sivakamasundari Vijayakumar & Roberta Sala & Gugene Kang & Angela Chen & Michelle Ann Pablo & Abidemi Ismail Adebayo & Andrea Cipriano & Jonas L. Fowler & Danielle L. Gomes & Lay Teng Ang & Kyle M. Lo, 2023. "Monolayer platform to generate and purify primordial germ-like cells in vitro provides insights into human germline specification," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    6. Brian DeVeale & Leqian Liu & Ryan Boileau & Jennifer Swindlehurst-Chan & Bryan Marsh & Jacob W. Freimer & Adam Abate & Robert Blelloch, 2022. "G1/S restriction point coordinates phasic gene expression and cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Yasuaki Uehara & Yusuke Tanaka & Shuyang Zhao & Nikolaos M. Nikolaidis & Lori B. Pitstick & Huixing Wu & Jane J. Yu & Erik Zhang & Yoshihiro Hasegawa & John G. Noel & Jason C. Gardner & Elizabeth J. K, 2023. "Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. J. McClatchy & R. Strogantsev & E. Wolfe & H. Y. Lin & M. Mohammadhosseini & B. A. Davis & C. Eden & D. Goldman & W. H. Fleming & P. Conley & G. Wu & L. Cimmino & H. Mohammed & A. Agarwal, 2023. "Clonal hematopoiesis related TET2 loss-of-function impedes IL1β-mediated epigenetic reprogramming in hematopoietic stem and progenitor cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    9. Ci Fu & Xiang Zhang & Amanda O. Veri & Kali R. Iyer & Emma Lash & Alice Xue & Huijuan Yan & Nicole M. Revie & Cassandra Wong & Zhen-Yuan Lin & Elizabeth J. Polvi & Sean D. Liston & Benjamin VanderSlui, 2021. "Leveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    10. Junyi Chen & Xiaoying Wang & Anjun Ma & Qi-En Wang & Bingqiang Liu & Lang Li & Dong Xu & Qin Ma, 2022. "Deep transfer learning of cancer drug responses by integrating bulk and single-cell RNA-seq data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. Kotaro Shimizu & Junichi Kikuta & Yumi Ohta & Yutaka Uchida & Yu Miyamoto & Akito Morimoto & Shinya Yari & Takashi Sato & Takefumi Kamakura & Kazuo Oshima & Ryusuke Imai & Yu-Chen Liu & Daisuke Okuzak, 2023. "Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    12. Young Hee Lee & Yu-Been Kim & Kyu Sik Kim & Mirae Jang & Ha Young Song & Sang-Ho Jung & Dong-Soo Ha & Joon Seok Park & Jaegeon Lee & Kyung Min Kim & Deok-Hyeon Cheon & Inhyeok Baek & Min-Gi Shin & Eun, 2023. "Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    13. Sandra Curras-Alonso & Juliette Soulier & Thomas Defard & Christian Weber & Sophie Heinrich & Hugo Laporte & Sophie Leboucher & Sonia Lameiras & Marie Dutreix & Vincent Favaudon & Florian Massip & Tho, 2023. "An interactive murine single-cell atlas of the lung responses to radiation injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    14. Seung-Hyun Jung & Byung-Hee Hwang & Sun Shin & Eun-Hye Park & Sin-Hee Park & Chan Woo Kim & Eunmin Kim & Eunho Choo & Ik Jun Choi & Filip K. Swirski & Kiyuk Chang & Yeun-Jun Chung, 2022. "Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2hi macrophages in infarcted hearts," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    15. Hailun Zhu & Sihai Dave Zhao & Alokananda Ray & Yu Zhang & Xin Li, 2022. "A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    16. Luke Simpson & Andrew Strange & Doris Klisch & Sophie Kraunsoe & Takuya Azami & Daniel Goszczynski & Triet Minh & Benjamin Planells & Nadine Holmes & Fei Sang & Sonal Henson & Matthew Loose & Jennifer, 2024. "A single-cell atlas of pig gastrulation as a resource for comparative embryology," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    17. Chih-Hao Wang & Tadataka Tsuji & Li-Hong Wu & Cheng-Ying Yang & Tian Lian Huang & Mari Sato & Farnaz Shamsi & Yu-Hua Tseng, 2024. "Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    18. Shuai Yan & Anna Santoro & Micah J. Niphakis & Antonio M. Pinto & Christopher L. Jacobs & Rasheed Ahmad & Radu M. Suciu & Bryan R. Fonslow & Rachel A. Herbst-Graham & Nhi Ngo & Cassandra L. Henry & Dy, 2024. "Inflammation causes insulin resistance in mice via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    19. Qingtao Sun & Daniëlle Lisdonk & Miriam Ferrer & Bruno Gegenhuber & Melody Wu & Youngkyu Park & David A. Tuveson & Jessica Tollkuhn & Tobias Janowitz & Bo Li, 2024. "Area postrema neurons mediate interleukin-6 function in cancer cachexia," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    20. Hannah Drew Rickner & Lulu Jiang & Rui Hong & Nicholas K. O’Neill & Chromewell A. Mojica & Benjamin J. Snyder & Lushuang Zhang & Dipan Shaw & Maria Medalla & Benjamin Wolozin & Christine S. Cheng, 2022. "Single cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model," Nature Communications, Nature, vol. 13(1), pages 1-22, 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_s41467-024-48914-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.