Biology subjects

Ostgaard, C. M.

Publications and source records attributed to Ostgaard, C. M..

2 recordsLinked to original sources

bioRxiv2025

A double-assurance mechanism restrains generation of high potential transit-amplifying progenitors during neurogenesis

Stem cells can generate differentiated progeny directly or indirectly through transit-amplifying progenitors (TAPs), which are vulnerable to tumorigenic transformation. Despite clinical relevance, how stem cells regulate TAP production is unclear. Drosophila brains contain Asense+ stem cells (Type1 neuroblasts; T1NBs) that generate low neurogenic potential TAPs and Asense- stem cells (Type2 neuroblasts; T2NBs) that produce high-potential TAPs [Intermediate Neural Progenitors (INPs)]. Unexpectedly, cell-type-specific enhancers of genes essential for INP formation are poised in T1NBs despite never generating INP progeny. Thus, both NB types are competent to generate INPs. Inducing T1NBs to generate INPs is more efficient upon asense knockdown. The progeny of T2NBs expressing elevated Asense adopt a low-potential TAP identity instead of INPs. Elevated Asense expression limits tumor NB expansion driven by stalled INPs halting tumor expansion. We propose that a double-assurance mechanism characterized by dynamic superimposition of lineage-specific activators upon basal-state determinants defines NB capability to generate high-potential TAPs.

developmental biology↗

bioRxiv2021

Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila

During Drosophila embryogenesis, the essential pioneer factor Zelda defines hundreds of cis-regulatory regions and in doing so reprograms the zygotic transcriptome. While Zelda is essential later in development, it is unclear how the ability of Zelda to define cis-regulatory regions is shaped by cell-type-specific chromatin architecture. Asymmetric division of neural stem cells (neuroblasts) in the fly brain provide an excellent paradigm for investigating the cell-type-specific functions of this pioneer factor. We show that Zelda synergistically functions with Notch to maintain neuroblasts in an undifferentiated state. Zelda misexpression reprograms progenitor cells to neuroblasts, but this capacity is limited by transcriptional repressors critical for progenitor commitment. Zelda genomic occupancy in neuroblasts is reorganized as compared to the embryo, and this reorganization is driven by differences in chromatin accessibility and cofactor availability. We propose that Zelda regulates essential transitions in the neuroblasts and embryo through a shared gene-regulatory network by defining cell-type-specific enhancers.

developmental biology↗