Date of Award

January 2024

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Silvia Vilarinho

Abstract

Single-cell RNA-sequencing (scRNA-seq) has enabled researchers to obtain data on gene expression at the previously unattainable single-cell level. To date, fetal liver studies have largely focused on characterizing fetal extramedullary hematopoiesis and less is known about the characterization of non-hematopoietic fetal liver cell types. Our knowledge of liver development is primarily based on studies using model organisms or human induced pluripotent stem cell in vitro model systems, rather than directly using human fetal liver specimen(s). In this project, I aim to develop a human fetal liver single-cell gene expression atlas that can provide insights into the development of hepatoblasts, endothelial cells, hepatic stellate cells, and mononuclear phagocytes, which include Kupffer cells. For that purpose, I aggregated and integrated four single-cell RNA sequencing datasets, which contain fifty-four unique fetal livers, encompassing 287,669 cells and spanning the ages of five to seventeen post-conception weeks. Data filtering and analysis was performed with R package Seurat v3. Manual annotation of processed data reveals 35,739 hepatoblasts, 14,754 endothelial cells, 9,367 hepatic stellate cells, 51,789 mononuclear phagocytes including Kupffer cells, and 95,370 other cells belonging to hematopoietic cell types. Integration and analysis of hepatoblasts reveal distinct developmental trajectories related to conception age.This project has the potential to be an informative tool for researchers as it offers insights at the single-cell level into fetal liver development and provides a valuable resource to examine gene expression of specific genes of interest across different fetal liver cell populations. I plan to create a web-page making this gene expression atlas accessible to other researchers studying fetal liver development.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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