METABOLIC PROGRAMS AS DETERMINANTS OF NEURAL PROGENITOR STATE AND HETEROGENEITY

During cortical development, neural progenitor cells (NPCs) dynamically balance proliferation and differentiation to ensure proper formation of the cerebral cortex. Early on, apical radial glial cells (aRGCs) expand the progenitor pool through symmetric divisions, before switching to asymmetric divisions that generate diverse progenitor types, specifically, basal RGCs and intermediate progenitors (IP). These cell fate transitions are accompanied by shifts in cellular metabolism, yet how metabolic programs are coordinated with transcriptional programs and cell-state transition defining NPC identity and spation organization in the developing cortex remains unclear. Preliminary spatial metabolic profiling of mouse embryonic brain tissues at embryonic (E) day 12.5 and 17.5 reveals distinct spatial metabolite patterns across developmental stages. From the Leiden clusters, there are 15 clusters. E17.5 mouse brain is composed of 3 clusters, while E12.5 mouse brain tissue is composed of the rest of the clusters. This result highlights the importance of regional metabolic regulation, especially in the ventricular zone, where the NPCs are enriched. Therefore, I aim to determine how metabolic states are linked to NPC identity and location, and whether metabolic differences between aRGCs, bRGCs, and IPs reflect progenitor cell state reflect progenitor cell state or the surrounding tissue environment. By integrating spatial metabolomic and single-cell transcriptomic analyses from the same developing mouse brain, this work will provide new insight into how metabolism supports neural progenitor expansion and differentiation during early brain development.