STUDYING CELLULAR DIVERSITY OF NEURAL PROGENITORS

The neurogenic potential of astrocytes outside of the two canonical adult neurogenic niches (the subventricular zone (SVZ) and the subgranular zone (SGZ)) remains debated. To investigate this potential and the molecular mechanisms involved, we used mouse embryonic stem cells (mESCs) as an in vitro model to corticogenesis, spanning early neurogenesis to late astrogliogenesis. We focused on BMP signaling, modulating its activation with fetal bovine serum, a physiological source of BMP4, during defined developmental windows. Early serum exposure biased differentiation toward a glial fate, increasing the proportion of GFAP⁺ cells compared to neurons. Prolonged serum treatment and passaging enriched the culture whit Sox9⁺/Map2⁻ progenitor-like astrocytic cells. Remarkably, these cells retained neurogenic competence; and were able to differentiate into Map2⁺ and NeuN⁺ neurons upon serum withdrawal or pharmacological BMP inhibition using LDN193189. To assess lineage progression more precisely, we are conducting a longitudinal study based on SATB2/CTIP2 expression ratios, reflecting the balance between upper- and deep-layer cortical neurons. This will be coupled with bulk RNA sequencing of neomycin-resistant progenitors treated at different developmental stages. Ongoing work includes experiments using spatially controlled Noggin gradients in confined culture systems to further dissect the role of BMP inhibition in regulating astrocyte plasticity. Together, our findings suggest that continuous BMP signaling promotes and stabilizes astrocytic identity but does not eliminate the latent neurogenic potential of astrocyte-like progenitors. This highlights the importance of BMP signaling dynamics in regulating neural lineage competence and provides insights into possible strategies for neural regeneration and reprogramming