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 (Pdgfrα × DTA) or mice lacking FAP-derived CSF1 (Pdgfrα × Csf1), 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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http://dx.doi.org/10.1038/s41467-023-43579-3 | DOI Listing |
Curr Top Dev Biol
April 2024
Department of Biochemistry, Faculty of Medicine and Health Sciences, McGill University, Montréal, QC, Canada; Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC, Canada. Electronic address:
Muscle stem cells (MuSCs) are crucial to the repair and homeostasis of mature skeletal muscle. MuSC dysfunction and dysregulation of the myogenic program can contribute to the development of pathology ranging from cancers like rhabdomyosarcoma (RMS) or muscle degenerative diseases such as Duchenne muscular dystrophy (DMD). Both diseases exhibit dysregulation at nearly all steps of myogenesis.
View Article and Find Full Text PDFNat Commun
December 2023
Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T1Z3, BC, Canada.
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.
View Article and Find Full Text PDFImmunity
September 2021
Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Ted Rogers Centre for Heart Research, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Peter Munk Cardiac Centre, Toronto, ON, Canada. Electronic address:
Hypertension affects one-third of the world's population, leading to cardiac dysfunction that is modulated by resident and recruited immune cells. Cardiomyocyte growth and increased cardiac mass are essential to withstand hypertensive stress; however, whether immune cells are involved in this compensatory cardioprotective process is unclear. In normotensive animals, single-cell transcriptomics of fate-mapped self-renewing cardiac resident macrophages (RMs) revealed transcriptionally diverse cell states with a core repertoire of reparative gene programs, including high expression of insulin-like growth factor-1 (Igf1).
View Article and Find Full Text PDFOncogene
April 2016
Department of Oncology and Children's Research Center, University Children's Hospital, Zurich, Switzerland.
Current treatment regimens for rhabdomyosarcoma (RMS), the most common pediatric soft tissue cancer, rely on conventional chemotherapy, and although they show clinical benefit, there is a significant risk of adverse side effects and secondary tumors later in life. Therefore, identifying and targeting sub-populations with higher tumorigenic potential and self-renewing capacity would offer improved patient management strategies. Hedgehog signaling has been linked to the development of embryonal RMS (ERMS) through mouse genetics and rare human syndromes.
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