PC1/3 deficiency impacts POMC processing in human embryonic stem cell-derived hypothalamic neurons

We developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof-of-principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both shRNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons. Overall design: We tried to idenitify transcripitional profiles and specific transcription factors that involved in of different stages during hypothalamic neuron differentiation from single cell sequencing for hESC-derived Day27 hypothalamic neurons, Day 12 neuron progenitors and undifferentiated stem cells

95

Wang L, Sui L, Panigrahi SK, Meece K, Xin Y, Kim J, Gromada J, Doege CA, Wardlaw SL, Egli D, Leibel RL