A pipeline for discovery-based research on human T cell development : integrating spatial omics and PSC-T cell platforms
department or school: Applied Science, Faculty of
department or school: Biomedical Engineering, School of
data provider: DSpace
degree campus: UBCV
creator: Stankiewicz, Laura
issued: 2024-12-10T19:06:58Z
issued: 2024
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: T cells play a critical role in adaptive immunity by recognizing self, versus non-self antigens, effectively protecting against pathogens and damaged or cancerous body cells. The application of T cells in cellular medicine to treat cancer and immunological disorders, as well as in personalized medicine to model disease pathologies, is rapidly expanding due to the potent role of T cells as mediators of the adaptive immune response. Pluripotent stem cell-derived T (PSC-T) cells have the potential to expand access to immunotherapies and disease modeling. However, current in vitro technologies have failed to recapitulate the signaling environments necessary to guide PSC-T cells towards mature helper and cytotoxic T cells in defined, feeder-free culture systems. T cells develop in the thymus, an organ specialized to support stage-specific T cell training via organization into spatially-defined niches. Previously, understanding of human T cell development and thymus niche biology was limited to interpretations from experimental animal models and observational learnings from patient populations with genetic mutations. These interpretations have proven challenging to adapt for in vitro PSC-T cell culture technology development. Here, we employ closed-loop learning to probe human T cell development. We first apply spatial multiomic technologies to create a spatially-defined map of tissue niches guiding T cell development in human postnatal thymus. We then test key insights into thymus niche biology in vitro using our PSC-T cell differentiation platform, demonstrating how our in vivo reference can be applied in vitro to guide T-lineage branching towards mature helper and cytotoxic PSC-T cells. Finally, we use our PSC-T platform to discover novel insights into the contribution of T cell receptor specificity to T-lineage branching. An additional insight from this work is how sex-based differences in thymus regulation and T cell development arise, and the potential for PSC-T pla…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/89816
note: A pipeline for discovery-based research on human T cell development: integrating spatial omics and PSC-T cell platforms by Laura Stankiewicz BASc, Queenâs University, 2019 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Biomedical Engineering) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) December 2024 © Laura Stankiewicz, 2024 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: A pipeline for discovery-based research on human T cell development: Integrating spatial omics and PSC-T cell platforms submitted by Laura Stankiewicz in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Biomedical Engineering Examining Committee: Fabio Rossi, Professor, Biomedical Engineering, University of British Columbia Co-supervisor Peter Zandstra, Professor, Biomedical Engineering, University of British Columbia Co-supervisor Ninan Abraham, Professor, Microbiology and Immunology, University of British Columbia Supervisory Committee Member Elizabeth Rideout, Associate Professor, Cellular & Physiological Sciences, University of British Columbia University Examiner Laura Evgin, Assistant Professor, Medical Genetics, University of British Columbia University Examiner Darrol Irvine, Professor, Biological Engineering and Materials Science & Engineering, Massachusetts Institute of Technology External Examiner Additional Supervisory Committee Members: Megan Levings, Professor, Biomedical Engineering, University of British Columbia Supervisory Committee Member Ali Bashashati, Assistant Professor, Biomedical Engineering, University of British Columbia Supervisory Committee Member iii Abstract T cells play a critical role in adaptive immunity by recognizing self, versus non-self antigens, effectively protecting against pathogens and damaged or ca…
has type: Thesis/Dissertation
date issued: 2025-05
is shown at: 10.14288/1.0447445
language: eng
degree discipline: Biomedical Engineering
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Rossi, Fabio M. V.
contributor: Zandstra, Peter
type: Text
identifier URI: http://hdl.handle.net/2429/89816