Transcriptome Analysis Did Not Show Endogenous Stem Cell Characteristics in Murine Lgr5⁺ Retinal Cells

Area of Science:

• Neuroscience
• Developmental Biology
• Stem Cell Biology

Background:

• Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is a known marker for intestinal adult stem cells.
• Lgr5 expression has recently been identified in neuronal tissues, including the retina.
• The precise role and identity of Lgr5-expressing cells in the retina remain unclear.

Purpose of the Study:

• To investigate whether retinal Lgr5-expressing cells possess properties of neural stem cells (NSC) or differentiated interneurons.
• To characterize the molecular profile of Lgr5+ retinal cells during development.

Main Methods:

• Isolation of Lgr5+ and Lgr5- retinal cell populations from postnatal day 5 and adult Lgr5EGFP-Ires-CreERT2 knock-in mice using fluorescence-activated cell sorting (FACS).
• Transcriptome analysis of sorted cell populations.
• Gene Ontology (GO) term enrichment analysis using the PANTHER platform to identify overrepresented biological processes.

Main Results:

• Transcriptome analysis did not identify enriched GO terms associated with NSC maintenance or proliferation in Lgr5+ retinal cells.
• Conversely, NSC maintenance and proliferation markers were prevalent in the Lgr5- retinal cell population.
• Wnt signaling pathways, often associated with stem cell maintenance, were not found to be active in Lgr5+ retinal cells.
• Gene expression profiles of Lgr5+ cells indicated they are differentiated neurons, specifically glycinergic amacrine cells.

Conclusions:

• Retinal Lgr5+ cells do not exhibit characteristics of neural stem cells.
• The findings strongly suggest that Lgr5+ cells in the retina represent a differentiated neuronal population, namely glycinergic amacrine cells.
• This study refines the understanding of Lgr5 function and cell identity within the developing and adult retina.