Publications by authors named "Pei-Ciao Tang"

11 Publications

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Usher Syndrome in the Inner Ear: Etiologies and Advances in Gene Therapy.

Int J Mol Sci 2021 Apr 10;22(8). Epub 2021 Apr 10.

Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

Hearing loss is the most common sensory disorder with ~466 million people worldwide affected, representing about 5% of the population. A substantial portion of hearing loss is genetic. Hearing loss can either be non-syndromic, if hearing loss is the only clinical manifestation, or syndromic, if the hearing loss is accompanied by a collage of other clinical manifestations. Usher syndrome is a syndromic form of genetic hearing loss that is accompanied by impaired vision associated with retinitis pigmentosa and, in many cases, vestibular dysfunction. It is the most common cause of deaf-blindness. Currently cochlear implantation or hearing aids are the only treatments for Usher-related hearing loss. However, gene therapy has shown promise in treating Usher-related retinitis pigmentosa. Here we review how the etiologies of Usher-related hearing loss make it a good candidate for gene therapy and discuss how various forms of gene therapy could be applied to Usher-related hearing loss.
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http://dx.doi.org/10.3390/ijms22083910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068832PMC
April 2021

Progress in Modeling and Targeting Inner Ear Disorders with Pluripotent Stem Cells.

Stem Cell Reports 2020 06 21;14(6):996-1008. Epub 2020 May 21.

Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address:

Sensorineural hearing loss and vestibular dysfunction are caused by damage to neurons and mechanosensitive hair cells, which do not regenerate to any clinically relevant extent in humans. Several protocols have been devised to direct pluripotent stem cells (PSCs) into inner ear hair cells and neurons, which display many properties of their native counterparts. The efficiency, reproducibility, and scalability of these protocols are enhanced by incorporating knowledge of inner ear development. Modeling human diseases in vitro through genetic manipulation of PSCs is already feasible, thereby permitting the elucidation of mechanistic understandings of a wide array of disease etiologies. Early studies on transplantation of PSC-derived otic progenitors have been successful in certain animal models, yet restoration of function and long-term cell survival remain unrealized. Through further research, PSC-based approaches will continue to revolutionize our understanding of inner ear biology and contribute to the development of therapeutic treatments for inner ear disorders.
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http://dx.doi.org/10.1016/j.stemcr.2020.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355141PMC
June 2020

Defective Tmprss3-Associated Hair Cell Degeneration in Inner Ear Organoids.

Stem Cell Reports 2019 07 13;13(1):147-162. Epub 2019 Jun 13.

Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address:

Mutations in the gene encoding the type II transmembrane protease 3 (TMPRSS3) cause human hearing loss, although the underlying mechanisms that result in TMPRSS3-related hearing loss are still unclear. We combined the use of stem cell-derived inner ear organoids with single-cell RNA sequencing to investigate the role of TMPRSS3. Defective Tmprss3 leads to hair cell apoptosis without altering the development of hair cells and the formation of the mechanotransduction apparatus. Prior to degeneration, Tmprss3-KO hair cells demonstrate reduced numbers of BK channels and lower expressions of genes encoding calcium ion-binding proteins, suggesting a disruption in intracellular homeostasis. A proteolytically active TMPRSS3 was detected on cell membranes in addition to ER of cells in inner ear organoids. Our in vitro model recapitulated salient features of genetically associated inner ear abnormalities and will serve as a powerful tool for studying inner ear disorders.
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http://dx.doi.org/10.1016/j.stemcr.2019.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626982PMC
July 2019

Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids.

Cell Rep 2018 01;22(1):242-254

Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address:

The mammalian hair follicle arises during embryonic development from coordinated interactions between the epidermis and dermis. It is currently unclear how to recapitulate hair follicle induction in pluripotent stem cell cultures for use in basic research studies or in vitro drug testing. To date, generation of hair follicles in vitro has only been possible using primary cells isolated from embryonic skin, cultured alone or in a co-culture with stem cell-derived cells, combined with in vivo transplantation. Here, we describe the derivation of skin organoids, constituting epidermal and dermal layers, from a homogeneous population of mouse pluripotent stem cells in a 3D culture. We show that skin organoids spontaneously produce de novo hair follicles in a process that mimics normal embryonic hair folliculogenesis. This in vitro model of skin development will be useful for studying mechanisms of hair follicle induction, evaluating hair growth or inhibitory drugs, and modeling skin diseases.
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http://dx.doi.org/10.1016/j.celrep.2017.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806130PMC
January 2018

Improved autologous cortical bone harvest and viability with 2Flute otologic burs.

Laryngoscope 2018 01 12;128(1):E40-E46. Epub 2017 Jul 12.

Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.

Objectives: To determine if 2Flute (Stryker Corporation, Kalamazoo, MI) otologic burs improve the size, cellular content, and bone healing of autologous cortical bone grafts harvested during canal wall reconstruction (CWR) tympanomastoidectomy with mastoid obliteration.

Study Design: Institutional review board-approved prospective cohort study.

Methods: Human autologous cortical bone chips were harvested using various burs (4 and 6 mm diameter; multiflute, and 2Flute [Stryker Corporation]) from patients undergoing CWR tympanomastoidectomy for the treatment of chronic otitis media with cholesteatoma. Bone chip size, cell counts, cellular gene expression, and new bone formation were quantified.

Results: Bone chips were significantly larger when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (113 ± 14 μm vs. 66 ± 8 μm ; P < 0.05) and 4 mm diameter (70 ± 8 μm vs. 50 ± 3 μm ; P < 0.05). After 2 weeks in culture, cell numbers were significantly higher when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (48.7 ± 3 vs. 31.8 ± 3 cells/μg bone; P < 0.05) and 4 mm diameter (27.6 ± 1.2 vs. 8.8 ± 1.2 cells/μg bone; P < 0.05). Bone-derived cells express osteoblast markers (alkaline phosphatase, osteocalcin). Cultured cells are able to form new bone in culture, and bone formation is facilitated by the presence of bone chips.

Conclusion: Use of 2Flute (Stryker Corporation) otologic burs for human autologous cortical bone harvest results in more viable bone fragments, with larger bone chips and more osteoblasts. Future studies are needed to determine if this leads to improved bone healing.

Level Of Evidence: NA. Laryngoscope, 128:E41-E46, 2018.
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http://dx.doi.org/10.1002/lary.26779DOI Listing
January 2018

Repair of traumatized mammalian hair cells via sea anemone repair proteins.

J Exp Biol 2016 08;219(Pt 15):2265-70

Department of Biology, University of Louisiana at Lafayette, Lafayette, LA 70503, USA

Mammalian hair cells possess only a limited ability to repair damage after trauma. In contrast, sea anemones show a marked capability to repair damaged hair bundles by means of secreted repair proteins (RPs). Previously, it was found that recovery of traumatized hair cells in blind cavefish was enhanced by anemone-derived RPs; therefore, the ability of anemone RPs to assist recovery of damaged hair cells in mammals was tested here. After a 1 h incubation in RP-enriched culture media, uptake of FM1-43 by experimentally traumatized murine cochlear hair cells was restored to levels comparable to those exhibited by healthy controls. In addition, RP-treated explants had significantly more normally structured hair bundles than time-matched traumatized control explants. Collectively, these results indicate that anemone-derived RPs assist in restoring normal function and structure of experimentally traumatized hair cells of the mouse cochlea.
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http://dx.doi.org/10.1242/jeb.135459DOI Listing
August 2016

Proteomic identification of hair cell repair proteins in the model sea anemone Nematostella vectensis.

Hear Res 2015 Sep 14;327:245-56. Epub 2015 Jul 14.

Department of Biology, University of Louisiana Lafayette, USA. Electronic address:

Sea anemones have an extraordinary capability to repair damaged hair bundles, even after severe trauma. A group of secreted proteins, named repair proteins (RPs), found in mucus covering sea anemones significantly assists the repair of damaged hair bundle mechanoreceptors both in the sea anemone Haliplanella luciae and the blind cavefish Astyanax hubbsi. The polypeptide constituents of RPs must be identified in order to gain insight into the molecular mechanisms by which repair of hair bundles is accomplished. In this study, several polypeptides of RPs were isolated from mucus using blue native PAGE and then sequenced using LC-MS/MS. Thirty-seven known polypeptides were identified, including Hsp70s, as well as many polypeptide subunits of the 20S proteasome. Other identified polypeptides included those involved in cellular stress responses, protein folding, and protein degradation. Specific inhibitors of Hsp70s and the 20S proteasome were employed in experiments to test their involvement in hair bundle repair. The results of those experiments suggested that repair requires biologically active Hsp70s and 20S proteasomes. A model is proposed that considers the function of extracellular Hsp70s and 20S proteasomes in the repair of damaged hair cells.
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http://dx.doi.org/10.1016/j.heares.2015.07.005DOI Listing
September 2015

Cadherin-23 may be dynamic in hair bundles of the model sea anemone Nematostella vectensis.

PLoS One 2014 22;9(1):e86084. Epub 2014 Jan 22.

Department of Biology, University of Louisiana at Lafayette, Lafayette, Louisiana, United States of America.

Cadherin 23 (CDH23), a component of tip links in hair cells of vertebrate animals, is essential to mechanotransduction by hair cells in the inner ear. A homolog of CDH23 occurs in hair bundles of sea anemones. Anemone hair bundles are located on the tentacles where they detect the swimming movements of nearby prey. The anemone CDH23 is predicted to be a large polypeptide featuring a short exoplasmic C-terminal domain that is unique to sea anemones. Experimentally masking this domain with antibodies or mimicking this domain with free peptide rapidly disrupts mechanotransduction and morphology of anemone hair bundles. The loss of normal morphology is accompanied, or followed by a decrease in F-actin in stereocilia of the hair bundles. These effects were observed at very low concentrations of the reagents, 0.1-10 nM, and within minutes of exposure. The results presented herein suggest that: (1) the interaction between CDH23 and molecular partners on stereocilia of hair bundles is dynamic and; (2) the interaction is crucial for normal mechanotransduction and morphology of hair bundles.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086084PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899209PMC
November 2014

Development of gene expression markers of acute heat-light stress in reef-building corals of the genus Porites.

PLoS One 2011 26;6(10):e26914. Epub 2011 Oct 26.

The University of Texas at Austin, Austin, Texas, United States of America.

Coral reefs are declining worldwide due to increased incidence of climate-induced coral bleaching, which will have widespread biodiversity and economic impacts. A simple method to measure the sub-bleaching level of heat-light stress experienced by corals would greatly inform reef management practices by making it possible to assess the distribution of bleaching risks among individual reef sites. Gene expression analysis based on quantitative PCR (qPCR) can be used as a diagnostic tool to determine coral condition in situ. We evaluated the expression of 13 candidate genes during heat-light stress in a common Caribbean coral Porites astreoides, and observed strong and consistent changes in gene expression in two independent experiments. Furthermore, we found that the apparent return to baseline expression levels during a recovery phase was rapid, despite visible signs of colony bleaching. We show that the response to acute heat-light stress in P. astreoides can be monitored by measuring the difference in expression of only two genes: Hsp16 and actin. We demonstrate that this assay discriminates between corals sampled from two field sites experiencing different temperatures. We also show that the assay is applicable to an Indo-Pacific congener, P. lobata, and therefore could potentially be used to diagnose acute heat-light stress on coral reefs worldwide.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026914PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202587PMC
March 2012

Assessing the impacts of experimentally elevated temperature on the biological composition and molecular chaperone gene expression of a reef coral.

PLoS One 2011 27;6(10):e26529. Epub 2011 Oct 27.

National Museum of Marine Biology and Aquarium, Checheng, Pingtung, Taiwan, ROC.

Due to the potential for increasing ocean temperatures to detrimentally impact reef-building corals, there is an urgent need to better understand not only the coral thermal stress response, but also natural variation in their sub-cellular composition. To address this issue, while simultaneously developing a molecular platform for studying one of the most common Taiwanese reef corals, Seriatopora hystrix, 1,092 cDNA clones were sequenced and characterized. Subsequently, RNA, DNA and protein were extracted sequentially from colonies exposed to elevated (30°C) temperature for 48 hours. From the RNA phase, a heat shock protein-70 (hsp70)-like gene, deemed hsp/c, was identified in the coral host, and expression of this gene was measured with real-time quantitative PCR (qPCR) in both the host anthozoan and endosymbiotic dinoflagellates (genus Symbiodinium). While mRNA levels were not affected by temperature in either member, hsp/c expression was temporally variable in both and co-varied within biopsies. From the DNA phase, host and Symbiodinium hsp/c genome copy proportions (GCPs) were calculated to track changes in the biological composition of the holobiont during the experiment. While there was no temperature effect on either host or Symbiodinium GCP, both demonstrated significant temporal variation. Finally, total soluble protein was responsive to neither temperature nor exposure time, though the protein/DNA ratio varied significantly over time. Collectively, it appears that time, and not temperature, is a more important driver of the variation in these parameters, highlighting the need to consider natural variation in both gene expression and the molecular make-up of coral holobionts when conducting manipulative studies. This represents the first study to survey multiple macromolecules from both compartments of an endosymbiotic organism with methodologies that reflect their dual-compartmental nature, ideally generating a framework for assessing molecular-level changes within corals and other endosymbioses exposed to changes in their environment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026529PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203140PMC
March 2012

Isolation and characteristics of 10 microsatellite markers from the endangered coconut crab (Birgus latro).

Mol Ecol Resour 2008 Nov 15;8(6):1448-50. Epub 2008 Sep 15.

Biodiversity Research Center, Academia Sinica, Nangang, Taipei 115, Taiwan.

The coconut crab (Birgus latro), an endangered marine-dispersed crustacean, is facing severe and probably accelerating population extinction worldwide, but biological information on its conservation remains deficient. In order to reveal the genetic structure of B. latro, 10 microsatellite loci were developed. A high degree of polymorphism was observed with a mean number of alleles per locus of 16.9. The mean expected heterozygosities were also high, ranging from 0.742 to 0.965. The observed heterozygosities ranged from 0.210 to 0.925. Departures from Hardy-Weinberg equilibrium were observed at five loci after the Bonferroni correction. These hypervariable markers will be utilized to study the genetic diversity and conservation of B. latro throughout its distribution range in the Pacific and Indian Oceans.
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http://dx.doi.org/10.1111/j.1755-0998.2008.02330.xDOI Listing
November 2008
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