Sstr2 Defines the Cone Differentiation-Competent Late-Stage Retinal Progenitor Cells in the Developing Mouse Retina

Area of Science:

• Neuroscience
• Ophthalmology
• Stem Cell Biology

Background:

• Cone cell death is a hallmark of several retinal degenerative diseases, leading to vision loss.
• Current stem cell therapies aim to replace photoreceptors, but identifying suitable retinal progenitor cells (RPCs) is challenging.
• Specific surface markers are needed to isolate RPCs with cone differentiation potential.

Purpose of the Study:

• To identify a surface marker for enriching late-stage RPCs capable of differentiating into cones.
• To evaluate the potential of Sstr2+ cells for cell transplantation in retinal degeneration models.

Main Methods:

• Single-cell RNA sequencing of developing mouse retinas.
• In vivo lineage tracing of Sstr2+ cells.
• In vitro differentiation assays of isolated Sstr2+ cells.
• Subretinal transplantation of Sstr2+ cells into wild-type and rd10 mice.

Main Results:

• Somatostatin receptor 2 (Sstr2) was identified as a surface marker highly expressed in late-stage RPCs.
• Sstr2+ cells differentiated into cones, amacrine, and horizontal cells in vivo.
• Isolated Sstr2+ cells exhibited RPC markers and cone differentiation potential in vitro.
• Transplanted Sstr2+ cells survived and expressed cone markers in recipient retinas.

Conclusions:

• Sstr2 effectively enriches late-stage RPCs primed for cone differentiation.
• Sstr2 serves as a valuable biomarker for isolating cone-generating RPCs for transplantation.
• This finding advances the development of stem cell therapies for retinal degenerative diseases.