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A nuclear hormone receptor and lipid metabolism axis are required for the maintenance and regeneration of reproductive organs

Shasha Zhang, Longhua Guo, Carlos Guerrero-Hernández, Eric J Ross, Kirsten Gotting, Sean A. McKinney, Wei Wang, Youbin Xiang, R. Scott Hawley, View ORCID ProfileAlejandro Sánchez Alvarado
doi: https://doi.org/10.1101/279364
Shasha Zhang
1Stowers Institute for Medical Research
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Longhua Guo
2University of California, Los Angeles
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Carlos Guerrero-Hernández
1Stowers Institute for Medical Research
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Eric J Ross
1Stowers Institute for Medical Research
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Kirsten Gotting
3University of Wisconsin, Madison
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Sean A. McKinney
1Stowers Institute for Medical Research
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Wei Wang
1Stowers Institute for Medical Research
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Youbin Xiang
1Stowers Institute for Medical Research
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R. Scott Hawley
1Stowers Institute for Medical Research
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Alejandro Sánchez Alvarado
1Stowers Institute for Medical Research
4Howard Hughes Medical Institute
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  • ORCID record for Alejandro Sánchez Alvarado
  • For correspondence: asa@stowers.org
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ABSTRACT

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 09, 2018.
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A nuclear hormone receptor and lipid metabolism axis are required for the maintenance and regeneration of reproductive organs
Shasha Zhang, Longhua Guo, Carlos Guerrero-Hernández, Eric J Ross, Kirsten Gotting, Sean A. McKinney, Wei Wang, Youbin Xiang, R. Scott Hawley, Alejandro Sánchez Alvarado
bioRxiv 279364; doi: https://doi.org/10.1101/279364
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A nuclear hormone receptor and lipid metabolism axis are required for the maintenance and regeneration of reproductive organs
Shasha Zhang, Longhua Guo, Carlos Guerrero-Hernández, Eric J Ross, Kirsten Gotting, Sean A. McKinney, Wei Wang, Youbin Xiang, R. Scott Hawley, Alejandro Sánchez Alvarado
bioRxiv 279364; doi: https://doi.org/10.1101/279364

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