Identification and Isolation of Human LGR5+ Cells Using an Antibody-Based Strategy

Methods Mol Biol. 2020:2171:3-23. doi: 10.1007/978-1-0716-0747-3_1.

Abstract

Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) has been identified as a marker of stem cells across multiple tissues. Lgr5-expressing cells are also regulators of tissue homeostasis and wound repair, and drivers of carcinogenic progression. The majority of information about Lgr5-expressing cells derives from genetically engineered mouse models. Human studies have been limited by a lack of specific reagents and experimental procedures for the purification of these cells. We recently demonstrated that antibody-based purification can be used to obtain viable LGR5-expressing cells from human primary tissues and patient derived organoids. Here, we provide detailed methods for the purification of these cells from colonic epithelial organoids generated from patient-derived tissues, from induced pluripotent stem cell (iPSC) derived intestinal organoids, and from freshly isolated patient tissue intestinal crypts. These methods will facilitate experimental analysis of human LGR5-expressing cells in development, wound healing, and cancer.

Keywords: Antibody; Colon; Colonoid; Enteroid; Human; Intestine; Lgr5; MACS; Organoid; Stem cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Colon / cytology*
  • Flow Cytometry
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Mice
  • Organoids / cytology*
  • Organoids / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • LGR5 protein, human
  • Receptors, G-Protein-Coupled