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PERICYTE SUBTYPES AT THE INTERSECTION BETWEEN TISSUE REGENERATION AND PATHOLOGY

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abstract
Normal tissue homeostasis as well as tissue regeneration and repair after damage rely on resident stem cells. Incomplete regeneration in mammals has been attributed to an insufficient number of stem cells and a rapid fibro/adipocytic infiltration after wounding. Excessive scar formation compromises tissue function and can lead to organ failure. Cells called pericytes, located around blood vessels, act as stem cells. Some studies suggest that pericytes may contribute to regeneration in various organs as well as fibrous tissue and fat formation in response to aging and pathologies. Based on markers and morphology, pericytes have been identified as heterogeneous. However, the differentiation capability of pericyte subtypes has not yet been explored. Here we distinguish two bona fide pericyte subpopulations based on molecular markers, Nestin-GFP-/NG2-DsRed+/ PDGFRâ+ (type-1) and Nestin-GFP+/NG2-DsRed+/ PDGFRâ+ (type-2). This thesis characterizes heretofore their unknown specific roles. Only type-2 pericytes have the potential, under optimized culture conditions, to generate neural cells. Additionally, type-2 pericytes participate in muscle regeneration; while type-1 contribute to fat accumulation. Type-1 pericytes deposit fibrous tissue in an organ-dependent manner in response to tissue injury. Moreover, only type-2 pericytes participate in normal and pathological angiogenesis. Our discoveries provide novel central cellular targets susceptible to signaling manipulation and pharmacological modulation in many diseases. Based on this work, we expect to limit deleterious pericytes' functions while preserving their healthy functions.
subject
pathology
pericytes
skeletal muscle
stem cells
tissue regeneration
contributor
Birbrair, Alexander (author)
Delbono, Osvaldo (committee chair)
Delbono, Osvaldo (committee member)
Brosnihan, K. Bridget (committee member)
Oppenheim, Ronald W. (committee member)
Debinski, Waldemar (committee member)
Mintz, Akiva (committee member)
date
2014-09-10T08:35:15Z (accessioned)
2015-03-10T08:30:09Z (available)
2014 (issued)
degree
Neuroscience (discipline)
embargo
2015-3-10 (terms)
identifier
http://hdl.handle.net/10339/39384 (uri)
language
en (iso)
publisher
Wake Forest University
title
PERICYTE SUBTYPES AT THE INTERSECTION BETWEEN TISSUE REGENERATION AND PATHOLOGY
type
Dissertation

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