Systems approach to unravel lymphoid development in human bone marrow

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Abstract/Contents

Abstract
Hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM) are the source of life-long replenish of immune cells in the humans. Among multiple lineages, T cell, B cell, NK cell, and Innate lymphoid cell (ILC) are classified as lymphoid cells, based on their morphology and developmental origin. However, mainly due to the limited experimental manipulations for human hematopoiesis studies, lymphopoiesis in human bone marrow still remains elusive. To overcome the experimental limitations, we leveraged the systems approach to analyze healthy human BM HSPCs. We conducted a highly multiplexed single-cell proteomic screen to construct a comprehensive protein expression map of human BM HSPCs. From there, we identified several lymphoid progenitor populations by their lymphoid specific functional protein markers. The target populations were assessed for their epigenetic priming for lymphoid lineages by chromatin accessibility. Furthermore, we utilized the protein expression information to identify surface markers to enrich for the target population, prospectively isolated, and functionally validated their lymphoid potentials ex vivo. This multi-omic study exemplifies the integration of a high-dimensional single-cell study with experimental validations. Moreover, we provide a fine-mapped human lymphopoiesis landscape in human hematopoiesis.

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 Kim, Yeeun
Degree supervisor Bendall, Sean
Degree supervisor Greenleaf, William
Thesis advisor Bendall, Sean
Thesis advisor Greenleaf, William
Thesis advisor Davis, Mark
Thesis advisor Majeti, Ravindra
Degree committee member Davis, Mark
Degree committee member Majeti, Ravindra
Associated with Stanford University, School of Medicine
Associated with Stanford University, Department of Microbiology and Immunology

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Yeeun Kim.
Note Submitted to the Department of Microbiology and Immunology.
Thesis Thesis Ph.D. Stanford University 2023.
Location https://purl.stanford.edu/yn086nh4480

Access conditions

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

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