Mechanisms leading to adrenal cortex development and steroid synthesis in humans are poorly understood due to the paucity of model systems. In a new study led by Kotaro Sasaki, MD, PhD, in the School of Veterinary Medicine at the University of Pennsylvania, human fetal adrenal cortex specification processes were recapitulated through stepwise induction of human-induced pluripotent stem cells through posterior intermediate mesoderm-like and adrenocortical progenitor-like states to ultimately generate fetal zone adrenal-cortex-like cells (FZLCs), as evidenced by histomorphological, ultrastructural, and transcriptome features and adrenocorticotropic hormone (ACTH)-independent Δ5 steroid biosynthesis. The researchers believe these findings provide a framework for understanding and reconstituting human adrenocortical development in vitro, paving the way for cell-based therapies of adrenal insufficiency.
Read the full paper from the Sasaki lab in Developmental Cell.