Prospective isolation of human fibroadipogenic progenitors with CD73

Natalya A. Goloviznina, Ning Xie, Abhijit Dandapat, Paul A. Iaizzo, Michael Kyba

Research output: Contribution to journalArticlepeer-review

Abstract

Skeletal muscle relies on coordination between myogenic and non-myogenic interstitial cells for homeostasis and for regeneration and response to injury. Fibroadipogenic progenitors (FAPs) have recently been recognized as key modulators of signaling to promote myogenesis following injury. FAPs are also responsible for the fibrosis and fatty replacement of muscle tissue seen in many diseased states. While extensive use of surface markers to purify FAPs has been undertaken in the mouse system, in particular PDGFRA, markers for human FAPs are less well understood. Here, we show that CD73 can be used as a single positive marker to purify FAPs from the lineage-negative (CD45-neg, CD31-neg) fraction of skeletal muscle mononuclear cells. Although CD73 was previously found to be expressed in cultured myogenic cells, we find that this marker is only acquired upon culture and that the CD73+ fraction of human skeletal muscle has no myogenic activity. We show that Lin-neg CD73+ cells from human muscle undergo fat differentiation as well as fibrogenesis when exposed to appropriate activating signals in vitro. This simple single positive marker approach effectively enables isolation of human FAPs from fresh human skeletal muscle biopsies.

Original languageEnglish (US)
Article numbere04503
JournalHeliyon
Volume6
Issue number7
DOIs
StatePublished - Jul 2020

Bibliographical note

Funding Information:
M. Kyba was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases ( R01 AR055685 ). N. Goloviznina was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases ( F31 AR073642 ).

Publisher Copyright:
© 2020 The Author(s)

Keywords

  • CD73
  • Cell biology
  • Cell culture
  • Cell differentiation
  • FAPs
  • Human fibroadipogenic progenitors
  • Musculoskeletal system
  • Stem cell research

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