Hypothalamic and Cell-Specific Transcriptomes Unravel a Dynamic Neuropil Remodeling in Leptin-Induced and Typical Pubertal Transition in Female Mice
Xingfa Han,
Laura L. Burger,
David Garcia-Galiano,
Seokmin Sim,
Susan J. Allen,
David P. Olson,
Martin G. Myers, Jr.,
Carol F. Elias
Affiliations
Xingfa Han
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Isotope Research Lab, Sichuan Agricultural University, Ya'an 625014, China
Laura L. Burger
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
David Garcia-Galiano
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
Seokmin Sim
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
Susan J. Allen
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
David P. Olson
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI 48109, USA
Martin G. Myers, Jr.
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA
Carol F. Elias
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Gynecology and Obstetrics, University of Michigan, Ann Arbor, MI 48109, USA; Corresponding author
Summary: Epidemiological and genome-wide association studies (GWAS) have shown high correlation between childhood obesity and advance in puberty. Early age at menarche is associated with a series of morbidities, including breast cancer, cardiovascular diseases, type 2 diabetes, and obesity. The adipocyte hormone leptin signals the amount of fat stores to the neuroendocrine reproductive axis via direct actions in the brain. Using mouse genetics, we and others have identified the hypothalamic ventral premammillary nucleus (PMv) and the agouti-related protein (AgRP) neurons in the arcuate nucleus (Arc) as primary targets of leptin action in pubertal maturation. However, the molecular mechanisms underlying leptin's effects remain unknown. Here we assessed changes in the PMv and Arc transcriptional program during leptin-stimulated and typical pubertal development using overlapping analysis of bulk RNA sequecing, TRAP sequencing, and the published database. Our findings demonstrate that dynamic somatodendritic remodeling and extracellular space organization underlie leptin-induced and typical pubertal maturation in female mice.
