Single cell examination of the human placenta
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 |
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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 |
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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 |
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Genre | Text |
Bibliographic information
Statement of responsibility | Kayla C. Kobak. |
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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).
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