• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Melanocyte stem cell subpopulations show distinct pigmentation and regenerative potential

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Tandukar_umaryland_0373D_11208.pdf
    Embargo:
    2021-07-01
    Size:
    9.330Mb
    Format:
    PDF
    Download
    Author
    Tandukar, Bishal cc
    0000-0002-9650-1664
    Advisor
    Hornyak, Thomas
    Date
    2020
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Melanocyte stem cells (McSCs) are key components of the hair follicle (HF) stem cell system. They are derived from neural crest during embryogenesis and are responsible for regeneration of differentiated melanocytes during successive HF cycles. We have described McSC subsets that can be distinguished by CD34 expression. CD34+ McSCs are located within the bulge/lower permanent portion (LPP) while CD34- McSCs are in the secondary hair germ (SHG) during the resting stage (telogen). Whether these two cell subpopulations are maintained separately or exist in a developmental hierarchy is not yet known. The goal of my thesis is to explore whether (a) the two McSC subpopulations are functionally distinct, (b) if they are maintained independently throughout the HF cycle and (c) their role in generation of mature melanocytes. To study McSCs, we engineered the Dct-H2BGFP bitransgenic mouse. We confirm that this animal model accurately identifies melanoblasts, McSCs and mature melanocytes by constitutive GFP expression that can be regulated by doxycycline. Using our Dct-H2BGFP mouse, we compared the transcriptomes of bulge and SHG McSC subsets by genome-wide expression profiling (RNA-seq). This study, along with functional in vitro and in vivo assays, confirms that CD34+/bulge share characteristics of neural crest stem cells with multilineage potential while CD34-/SHG McSCs represent a stem cell population that is more committed to melanocyte differentiation. To further understand the relationship between two McSC subpopulations, we traced their proliferation throughout the HF cycle and found that proliferation of SHG McSCs gives rise to mature melanocytes. The analysis also surprisingly revealed quiescent CD34- melanocytes maintained outside of the HF bulge region throughout anagen retaining the stem cell phenotype, identifying a SHG McSC-like population outside telogen suggesting independent or quasi-independent maintenance of the two McSC subpopulations. Taken together, our study identifies heterogeneous McSC subpopulations with distinct pigmentation and regenerative potential for the first time. Strikingly, CD34+/bulge McSCs exhibited the ability to myelinate neurons in vivo, revealing a novel therapeutic possibility for demyelinating disorders and traumatic nerve injury.
    Description
    Biochemistry
    University of Maryland, Baltimore
    Ph.D.
    Keyword
    mouse model
    Hair Follicle
    Melanocytes
    Neural Crest
    Pigmentation
    Stem Cells
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14644
    Collections
    Theses and Dissertations School of Medicine
    Theses and Dissertations All Schools

    entitlement

     
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.