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

Farshad Babaeijandaghi (), Nasim Kajabadi, Reece Long, Lin Wei Tung, Chun Wai Cheung, Morten Ritso, Chih-Kai Chang, Ryan Cheng, Tiffany Huang, Elena Groppa, Jean X. Jiang and Fabio M. V. Rossi ()
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Farshad Babaeijandaghi: University of British Columbia
Nasim Kajabadi: University of British Columbia
Reece Long: University of British Columbia
Lin Wei Tung: University of British Columbia
Chun Wai Cheung: University of British Columbia
Morten Ritso: University of British Columbia
Chih-Kai Chang: University of British Columbia
Ryan Cheng: University of British Columbia
Tiffany Huang: University of British Columbia
Elena Groppa: University of British Columbia
Jean X. Jiang: University of Texas Health Science Center
Fabio M. V. Rossi: University of British Columbia

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43579-3

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