DPPIV+ fibro-adipogenic progenitors form the niche of adult skeletal muscle self-renewing resident macrophages

  • Nat Commun. 2023 Dec 13;14(1):8273. doi: 10.1038/s41467-023-43579-3.
Farshad Babaeijandaghi  #  1  2 ,  Nasim Kajabadi  #  3 ,  Reece Long  3 ,  Lin Wei Tung  3 ,  Chun Wai Cheung  3 ,  Morten Ritso  3 ,  Chih-Kai Chang  3 ,  Ryan Cheng  3 ,  Tiffany Huang  3 ,  Elena Groppa  3 ,  Jean X Jiang  4 ,  Fabio M V Rossi  5
Affiliations
  • 1. Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T1Z3, BC, Canada. [email protected].
  • 2. Altos Labs Inc, San Diego, CA, USA. [email protected].
  • 3. Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T1Z3, BC, Canada.
  • 4. Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, TX, USA.
  • 5. Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T1Z3, BC, Canada. [email protected].
  • # Contributed equally.
PMID: 38092736 DOI: 10.1038/s41467-023-43579-3
Abstract

Adult tissue-resident macrophages (RMs) are either maintained by blood monocytes or through self-renewal. While the presence of a nurturing niche is likely crucial to support the survival and function of self-renewing RMs, evidence regarding its nature is limited. Here, we identify fibro-adipogenic progenitors (FAPs) as the main source of colony-stimulating factor 1 (CSF1) in resting skeletal muscle. Using parabiosis in combination with FAP-deficient transgenic mice (PDGFRαCreERT2 × DTA) or mice lacking FAP-derived CSF1 (PDGFRαCreERT2 × Csf1flox/null), we show that local CSF1 from FAPs is required for the survival of both TIM4- monocyte-derived and TIM4+ self-renewing RMs in adult skeletal muscle. The spatial distribution and number of TIM4+ RMs coincide with those of Dipeptidyl Peptidase IV (DPPIV)+ FAPs, suggesting their role as CSF1-producing niche cells for self-renewing RMs. This finding identifies opportunities to precisely manipulate the function of self-renewing RMs in situ to further unravel their role in health and disease.

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