Single cell examination of the human placenta

Placeholder Show Content

Abstract/Contents

Abstract
The placenta, a vital organ for fetal development and species propagation, plays a crucial role in sustaining the fetus by providing nutrients, oxygen, and hormonal support. Despite extensive morphological descriptions, the molecular organization and characterization of cell types within the placenta remain limited. Recent advancements in single-cell RNA sequencing technologies have revealed various trophoblast and fetal cell subtypes, but the open-chromatin regulatory landscape has yet to be described. This dissertation aims to address this knowledge gap by employing a multi-dimensional approach, encompassing single-cell transcriptomics, epigenomics, and copy number variation (CNV) analysis. The study explores placental dynamics across the first trimester and compares them to the third trimester placenta, providing valuable insights into the cellular composition, differentiation trajectories, and regulatory landscape of early placental development. Utilizing single-cell transcriptomics, we identified three distinct syncytiotrophoblast subtypes in the first trimester placenta, each characterized by unique gene expression profiles and marker genes. We further created bulk open chromatin maps to identify active transcription factor motifs within different placental cell types and subtypes. By analyzing genetic variation and CNVs within the placental genome, we also gained insights into the potential influence of structural genomic alterations on the placental regulatory landscape and gene expression patterns. Our findings provide a comprehensive understanding of the modality within the placenta during the late first trimester, as placental cells adeptly respond to the establishment of maternal blood supply, facilitating nutrient and oxygen transfer to the developing fetus. The integration of single-cell transcriptomics, epigenomics, and CNV analysis in this study enhances our understanding of the intricate processes underlying placental development. These findings contribute to the broader knowledge of the placenta's critical role in pregnancy and its implications for maternal and fetal health. Moreover, the identification of specific CNVs and their integration with transcriptional and epigenetic regulation opens avenues for future investigations into the functional consequences of genetic variation, pregnancy complications, and potential therapeutic interventions.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2023; ©2023
Publication date 2023; 2023
Issuance monographic
Language English

Creators/Contributors

Author Kobak, Kayla Christian
Degree supervisor Baker, Julie, (Professor of genetics)
Thesis advisor Baker, Julie, (Professor of genetics)
Thesis advisor Boettiger, Alistair
Thesis advisor Kundaje, Anshul, 1980-
Thesis advisor Lipsick, Joseph Steven, 1955-
Degree committee member Boettiger, Alistair
Degree committee member Kundaje, Anshul, 1980-
Degree committee member Lipsick, Joseph Steven, 1955-
Associated with Stanford University, School of Medicine
Associated with Stanford University, Department of Genetics

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Kayla C. Kobak.
Note Submitted to the Department of Genetics.
Thesis Thesis Ph.D. Stanford University 2023.
Location https://purl.stanford.edu/dy320mh4187

Access conditions

Copyright
© 2023 by Kayla Christian Kobak
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

Also listed in

Loading usage metrics...