Doctoral thesis
OA Policy
English

Characterising the Development of Major Steroidogenic Organs Using Single-Cell RNA Sequencing

ContributorsSararols, Paulineorcid
DirectorsNef, Sergeorcid
Number of pages281
Imprimatur date2022-04-08
Defense date2022-04-08
Abstract

The adrenal glands and gonads are an important part of the endocrine system, as they are the two main steroidogenic organs in mammals. They play a pivotal role in the regulation of body fluid homeostasis, metabolism, immunity, inflammation, stress response, and sexual development and reproduction. Surprisingly, the gonads and adrenal glands share functional characteristics, expressing many of the same enzymes required to catalyse steroid synthesis, and in both organs, steroidogenesis is regulated by the hypothalamus-pituitary endocrine axis. These high similarities are explained by a common developmental origin, the adrenogonadal primordium (AGP), identified initially by the expression of Nr5a1, a specific marker of steroidogenic cells, in the coelomic epithelium. Hence, this primordium provides a unique model for studying cell fate decisions during mammalian morphogenesis. The small number of progenitor cells and the heterogeneity of cell types make emerging single cell technologies a preferred approach for investigations of cell differentiation by ensuring accurate characterisation of population diversity. Thus, we have generated a comprehensive atlas of the developing gonads and adrenals, using single cell time series transcriptomics. In this PhD thesis, I investigated cell fate decisions during steroidogenic cell differentiation in the developing adrenal cortex and gonads. First, I characterised the cellular identity of steroidogenic progenitor cells and described the molecular events involved during AGP formation, as well as during lineage specification leading to the separation of the adrenal and gonadal primordium. In the differentiated testis, I depicted the transcriptomic and functional differences between fetal and adult Leydig cells, which appear sequentially throughout life, and identified specific marker genes for both populations. In addition, I identified crucial differences in the regulation of steroidogenesis between fetal and adult Leydig cells. Finally, I investigated the fate of steroidogenic cells in the developing mouse adrenal cortex during the establishment of functional zones. This process, called zonation, results in the differentiation of steroidogenic cells, which are able to adopt a zona Glomerulosa or zona Fasciculata identity depending on their location in the cortex. Finally, the comprehensive atlas we have generated has allowed us to answer the preceding questions, but will also be a valuable resource for further studies. Thus, this atlas can improve the understanding of congenital diseases associated with adrenal and gonadal development.

Keywords
  • Single-cell RNA sequencing
  • Steroids
  • Steroidogenic organs
  • Adrenal gland
  • Testis
  • Development
Citation (ISO format)
SARAROLS, Pauline. Characterising the Development of Major Steroidogenic Organs Using Single-Cell RNA Sequencing. Doctoral Thesis, 2022. doi: 10.13097/archive-ouverte/unige:161101
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Creation26/05/2022 09:31:00
First validation26/05/2022 09:31:00
Update time21/03/2024 07:32:40
Status update21/03/2024 07:32:40
Last indexation01/10/2024 21:26:19
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