Da Costa, Maria José Minhoto Diniz (2019) Cellular heterogeneity of the human endometrium : transcriptomic deconvolution and characterization of stem/progenitor cells. PhD thesis, University of Warwick.

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Abstract

During a woman’s reproductive years the human endometrium becomes a highly dynamic tissue that sheds and regenerates on a cyclic basis. Apart from the main cell populations (i.e. stromal, endothelial, epithelial and immune cells), the endometrium also comprises a hierarchy of stem and more committed cells that are responsible for the remarkable regenerative ability of this tissue. This heterogeneity hinders the interpretation of bulk RNA-seq data and subsequently, the identification of specific stem cell transcriptomic signatures. Hence, the aim of this thesis was to assess and interpret endometrial heterogeneity with a focus on the characterization of stem/progenitor cells. Firstly, a reference matrix with the transcriptome profile of epithelial, uNK and stromal subpopulations was generated and used in the deconvolution of whole tissue transcriptome data across the menstrual cycle. This analysis showed that the transition from early- to mid-secretory is followed by an adjustment in the stromal:epithelial ratio. Additionally, it was demonstrated that endometrial mesenchymal stem cells (eMSC) encompass a heterogeneous population, and that their microenvironment may share common stemness properties with other adult stem cells.

Secondly, single cell RNA-seq was employed to analyse endometrial cell heterogeneity. Apart from stromal, endothelial, epithelial and diverse immune cell populations, a discrete population of highly proliferative mesenchymal cells was identified and further characterized. Through several lines of evidence, I demonstrated that these cells correspond to a putative progenitor cell population and that anillin is a candidate marker for endometrial clonogenicity.

Lastly, single-nucleus transcriptomic analysis was optimized for archived endometrial samples in order to bypass the disadvantages inherent to single cell approaches that are dependent on fresh tissues. In summary, this thesis contributed to the characterization of endometrial stem cell biology and identified a progenitor cell population that might be related to the decidua remodelling during pregnancy.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QH Natural history > QH301 Biology Q Science > QM Human anatomy Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Endometrium -- Physiology, Stem cells, Nucleotide sequence
Official Date:	November 2019
Dates:	Date Event November 2019 UNSPECIFIED
Institution:	University of Warwick
Theses Department:	Warwick Medical School
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Brosens, Jan J.
Sponsors:	Tommy's (Charity)
Format of File:	pdf
Extent:	xv, 185 leaves : illustrations (some colour)
Language:	eng

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