Defined populations of inner ear progenitor cells show limited and distinct capacities for differentiation into hair cells, neurons, and glia
Thesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, 2014.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2015
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| Online Access: | http://hdl.handle.net/1721.1/97320 |
| _version_ | 1826203911652900864 |
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| author | McLean, Will (Will James) |
| author2 | Ruth Anne Eatock and Albert Edge. |
| author_facet | Ruth Anne Eatock and Albert Edge. McLean, Will (Will James) |
| author_sort | McLean, Will (Will James) |
| collection | MIT |
| description | Thesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, 2014. |
| first_indexed | 2024-09-23T12:45:18Z |
| format | Thesis |
| id | mit-1721.1/97320 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T12:45:18Z |
| publishDate | 2015 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/973202019-04-12T09:30:16Z Defined populations of inner ear progenitor cells show limited and distinct capacities for differentiation into hair cells, neurons, and glia McLean, Will (Will James) Ruth Anne Eatock and Albert Edge. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. Thesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, 2014. Cataloged from PDF version of thesis. Includes bibliographical references (pages 66-74). Despite the fact that mammalian hair cells and neurons do not naturally regenerate in vivo, progenitor cells exist within the postnatal inner ear that can be manipulated to generate hair cells and neurons. This work reveals the differentiation capabilities of distinct inner ear progenitor populations and pinpoints cell types that can become cochlear hair cells, vestibular hair cells, neurons, and CNS glia. We expanded and differentiated cochlear and vestibular progenitors from mice (postnatal days 1-3) and analyzed the cells for expression of mature properties by RT-PCR, immunostaining, and patch clamping. Whereas previous reports suggested that inner ear stem cells may be pluripotent and/or revert to a more neural stem cell fate, we find that cells from each organ type differentiated into cells with characteristics of the respective organ. Only cochlear-derived cells expressed the outer-hair-cell protein, prestin, while only vestibular derived cells expressed the vestibular extracellular matrix marker, otopetrin. Since Atohi expression is consistently found in new hair cells, we used an Atohl-nGFP mouse line to identify hair cell candidates. We find that cells expressing Atohl also expressed key transduction, hair bundle, and synaptic genes needed for proper function. Whole-cell patch clamp recordings showed that Atoh1-nGFP+ cells derived from both cochlear and vestibular tissue had voltage gated ion channels that were typical of postnatal hair cells. Only vestibular-derived AtohinGFP+ cells, however, had Ih, a hyperpolarization-activated current typical of native vestibular hair cells but not native cochlear hair cells. Lineage tracing studies with known supporting cell and glial cell markers showed that progenitor capacity of cochlear supporting cells positive for Lgr5 (Lgr5+ cells) was limited to differentiation into hair cell-like cells but not neuron-like cells. In contrast, glial cells positive for PLP (PLP1+ cells) from the auditory nerve differentiated into multiple cell types, with properties of neurons, astrocytes, or mature oligodendrocytes but not hair cells. Thus, PLP+ progenitor cells within the auditory nerve are limited to neuronal or glial fates but have greater potency than Lgr5+ progenitors, which only formed hair cell-like cells. In summary, this work identifies distinct populations of post-natal inner ear progenitors and delineates their capacity for differentiation and maturation. by Will McLean. Ph. D. 2015-06-10T19:09:11Z 2015-06-10T19:09:11Z 2014 2014 Thesis http://hdl.handle.net/1721.1/97320 910257146 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 74 pages application/pdf Massachusetts Institute of Technology |
| spellingShingle | Harvard--MIT Program in Health Sciences and Technology. McLean, Will (Will James) Defined populations of inner ear progenitor cells show limited and distinct capacities for differentiation into hair cells, neurons, and glia |
| title | Defined populations of inner ear progenitor cells show limited and distinct capacities for differentiation into hair cells, neurons, and glia |
| title_full | Defined populations of inner ear progenitor cells show limited and distinct capacities for differentiation into hair cells, neurons, and glia |
| title_fullStr | Defined populations of inner ear progenitor cells show limited and distinct capacities for differentiation into hair cells, neurons, and glia |
| title_full_unstemmed | Defined populations of inner ear progenitor cells show limited and distinct capacities for differentiation into hair cells, neurons, and glia |
| title_short | Defined populations of inner ear progenitor cells show limited and distinct capacities for differentiation into hair cells, neurons, and glia |
| title_sort | defined populations of inner ear progenitor cells show limited and distinct capacities for differentiation into hair cells neurons and glia |
| topic | Harvard--MIT Program in Health Sciences and Technology. |
| url | http://hdl.handle.net/1721.1/97320 |
| work_keys_str_mv | AT mcleanwillwilljames definedpopulationsofinnerearprogenitorcellsshowlimitedanddistinctcapacitiesfordifferentiationintohaircellsneuronsandglia |