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Doctoral thesis
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Characterizing Mouse Sex Determination and Differentiation at the Single Cell Level

ContributorsMayere, Chloéorcid
DirectorsNef, Sergeorcid
Number of pages211
Imprimatur date2022-10-31
Defense date2022-10-31
Abstract

Sexual reproduction is the most frequent mode of reproduction in the animal and plant kingdoms. It requires the generation of specific gametes and specialized organs. During embryonic development, in vertebrates, the gonads develop from a common primordium. At about 6 weeks of development in humans and on the eleventh day of development in mice, depending on the presence of the SRY gene, the primordium acquires either an ovarian or a testicular fate. This is called gonadal sex determination. The gonads will then follow a specific transcriptional program allowing their differentiation into ovaries or testicles. The gonadal sex will then determine the primary sexual characteristics of the individual which are the internal and external genitalia. Then, at puberty, the steroid hormones produced by the gonads will lead to the acquisition of secondary sexual characteristics and will make the individual enter its reproductive life period. Sexual determination therefore requires that two organs with different morphologies and functions can develop from the same primordium, and that only one of the two destinies is retained and maintained according to the genetic sex of the individual. This is a unique phenomenon in developmental biology that requires the establishment of sex-specific genetic programs with three major functions. First, to allow the development and differentiation of the cell lineages present in the gonad according to the adopted fate. Second, to antagonize the genetic program of the opposite sex. Third, to maintain the gonadal sex throughout the life of the individual. However, there are still many grey areas. For example, we do not know exactly what populations are present in the gonad during development and what influences they might have on each other. Similarly, the origins of steroidogenic cells in the gonad are only incompletely described, and the transcriptomic mechanisms of germ cell sex determination are imperfectly described and subject to debate. In an attempt to address these questions and to study gonadal sex determination in an integrated manner, we took advantage of new single-cell RNA sequencing technologies and generated a comprehensive atlas of steroidogenic organ development and differentiation in the mouse. This atlas contains transcriptomes of approximately 150,000 cells including 100,000 from gonadal adrenal primordia and male and female gonads at several stages of embryonic development.

This PhD thesis presents a test and hypothesis generation work based on the analysis and exploration of this transcriptomic atlas. During this work, I was able to identify all the cell types present in the gonad during its development. I have analyzed and described in depth the genetic programs governing germ cell differentiation. I also described and characterized the origin and fate of a rare population, similar to the supporting cells, which gives rise to the rete testis and ovarii. Finally, I reconstructed the interstitial cell lineages of the testis that give rise to Leydig cells and peritubular myoid cells. This work has also been the occasion of several international collaborations dealing with many issues related to gonadal development.

eng
Keywords
  • Single Cell
  • RNA
  • Sequencing
  • Bioinformatic
  • Transcriptomic
  • Development
  • Sexual
  • Gonad
  • Ovary
  • Testis
  • Embryogenesis
  • Mouse
  • NGS
  • Atlas
  • Expression
  • Sertoli
  • Leydig
  • Granulosa
  • PAX8
  • Germ-cells
  • Meiosis
  • Sex determination
  • XX
  • XY
Citation (ISO format)
MAYERE, Chloé. Characterizing Mouse Sex Determination and Differentiation at the Single Cell Level. 2022. doi: 10.13097/archive-ouverte/unige:169456
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Creation06/09/2023 11:41:51 AM
First validation06/12/2023 9:11:02 AM
Update time06/12/2023 9:11:02 AM
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