RT Journal Article
SR Electronic
T1 A nuclear hormone receptor and lipid metabolism axis are required for the maintenance and regeneration of reproductive organs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 279364
DO 10.1101/279364
A1 Shasha Zhang
A1 Longhua Guo
A1 Carlos Guerrero-Hernández
A1 Eric J Ross
A1 Kirsten Gotting
A1 Sean A. McKinney
A1 Wei Wang
A1 Youbin Xiang
A1 R. Scott Hawley
A1 Alejandro Sánchez Alvarado
YR 2018
UL http://biorxiv.org/content/early/2018/03/09/279364.1.abstract
AB Understanding how stem cells and their progeny maintain and regenerate reproductive organs is of fundamental importance. The freshwater planarian Schmidtea mediterranea provides an attractive system to study these processes because its hermaphroditic reproductive system (RS) arises post-embryonically and when lost can be fully and functionally regenerated from the proliferation and regulation of experimentally accessible stem and progenitor cells. By controlling the function of a nuclear hormone receptor gene (nhr-1), we established conditions in which to study the formation, maintenance and regeneration of both germline and somatic tissues of the planarian RS. We found that nhr-1(RNAi) not only resulted in the gradual degeneration and complete loss of the adult hermaphroditic RS, but also in the significant downregulation of a large cohort of genes associated with lipid metabolism. One of these, Smed-acs-1, a homologue of Acyl-CoA synthetase, was indispensable for the development, maintenance and regeneration of the RS, but not for the homeostasis or regeneration of other somatic tissues. Remarkably, supplementing nhr-1(RNAi) animals with either bacterial Acyl-CoA synthetase or the lipid metabolite Acetyl-CoA rescued the phenotype restoring the maintenance and function of the hermaphroditic RS. Our findings uncovered a likely evolutionarily conserved role for nuclear hormone receptors and lipid metabolism in the regulation of stem and progenitor cells required for the long-term maintenance and regeneration of animal reproductive organs, tissues and cells.