A bifunctional optical reporter for tracking estrogen response dynamics in neurons

Area of Science:

• Neuroscience
• Endocrinology
• Molecular Biology

Background:

• Estrogens are crucial signaling molecules influencing physiology and behavior.
• Current methods for tracking estrogen dynamics in vivo lack tissue specificity and temporal resolution.
• Existing techniques do not capture the dynamic nature of estrogen response.

Purpose of the Study:

• To develop a novel bifunctional reporter, neuro-seeER, for tracking estrogen dynamics in vitro and in vivo.
• To enable real-time monitoring of estrogen action in specific cell populations.
• To investigate the heterogeneity of cellular and temporal transcriptional responses to estrogen.

Main Methods:

• Development of the neuro-seeER bifunctional reporter.
• Validation of neuro-seeER response specificity and timescale.
• Application of neuro-seeER in Esr1-Cre mice for hypothalamic estrogen dynamics.
• Utilizing snapshot photometry for longitudinal in vivo tracking.
• Fluorescence-aided cell sorting and RNA-sequencing.

Main Results:

• Neuro-seeER requires estrogen receptor expression and is activated by estradiol.
• Dynamic labeling of estrogen-responsive hypothalamic cells was observed.
• High neuro-seeER response correlates with enriched estrogen-responsive genes.
• Robust detection of exogenous estrogen response across multiple hypothalamic sites.
• Successful capture of endogenous estrogen response dynamics across the estrous cycle.

Conclusions:

• Neuro-seeER provides unprecedented temporal and spatial resolution for tracking estrogen dynamics in vivo.
• The tool reveals cellular and temporal heterogeneity in transcriptional responses to estrogen.
• Neuro-seeER facilitates simultaneous monitoring of hormonal dynamics with neural or behavioral measures.
• This technology opens new avenues for studying hormone action in complex biological systems.