University of Illinois Urbana-Champaign

Single-cell approaches to assess hematopoietic stem cell response to matrix cues

Choi, Ji Sun

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Ji Sun_Choi.pdf

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https://hdl.handle.net/2142/50399

Description

Title
Single-cell approaches to assess hematopoietic stem cell response to matrix cues
Author(s)
Choi, Ji Sun
Issue Date
2014-09-16
Director of Research (if dissertation) or Advisor (if thesis)
Harley, Brendan A.
Doctoral Committee Chair(s)
Harley, Brendan A.
Committee Member(s)
  • Cunningham, Brian T.
  • Kraft, Mary L.
  • Leckband, Deborah E.
Department of Study
Chemical & Biomolecular Engr
Discipline
Chemical Engineering
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2014-09-16T17:12:34Z
Keyword(s)
  • Hematopoietic stem cell
  • Single cell approach
  • Cell-matrix interactions
Abstract
Hematopoietic stem cells (HSC) are adult stem cells responsible for life-long hematopoiesis, the production of the full complement of blood and immune cells for hematological and immune systems. HSCs reside in the bone marrow within specialized microenvironments known as niches, comprised of various cellular and extracellular components including niche cells, extracellular matrix (ECM), and immobilized or soluble signaling molecules that provide extrinsic cues to regulate HSC fate decisions: quiescence, self-renewal, differentiation, mobilization, migration, retention, and apoptosis. Variations in structure and composition across the marrow niche microenvironments are believed to present combinations of signals that selectively regulate multiple stages of hematopoiesis. As predicted by such a hypothesis, HSCs exhibit dynamic behavior (e.g., mobilization, homing, migration) and localize non-uniformly within the marrow, with more primitive HSCs frequently localizing near the endosteum while less primitive, cycling progenitors associated with vascular sinusoids. The dynamic interplay between HSCs and a range of subregions within the bone marrow suggest that microenvironmental signals may be key regulators of HSC fate decisions. However, teasing apart the effect of niche-inspired biophysical cues on HSC fate decision processes have been challenging due to the rarity of HSCs within the marrow, our lack of technical ability to expand or differentiate HSCs freely in vitro, and a lack of available single cell metrics to continuously analyze the functional output of HSCs in situ. Our goal therefore is to build a multiplex in vitro culture platform that provides defined matrix cues while enabling label-free analysis of HSCs in situ. We first show that matrix cues do in fact directly impact HSC biophysical properties (Chapter 2) and fate decisions (Chapter 3) and identify a set of matrix cues that favor HSC self-renewal over lineage specification (Chapter 3). We then evaluate single cell analysis techniques (e.g., Raman Spectroscopy) as potential functional metrics for HSCs (Chapter 4). In particular, we assess the feasibility of using adhesive signatures of individual HSCs (e.g., Photonic crystal enhanced microscopy) as a new metric for monitoring their functional output (Chapter 5). Finally, we review our progress and discuss ongoing work and future opportunities (Conclusions).
Graduation Semester
2014-08
Permalink
http://hdl.handle.net/2142/50399
Copyright and License Information
Copyright 2014 Ji Sun Choi

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Dissertations and Theses - Chemical and Biomolecular Engineering