title: Nonviral Reprogramming of Human Wharton's Jelly Cells Reveals Differences Between ATOH1 Homologues.
abstract: The transcription factor atonal homolog 1 (ATOH1) has multiple homologues that are functionally conserved across species and is responsible for the generation of sensory hair cells. To evaluate potential functional differences between homologues, human and mouse ATOH1 (HATH1 and MATH-1, respectively) were nonvirally delivered to human Wharton's jelly cells (hWJCs) for the first time. Delivery of HATH1 to hWJCs demonstrated superior expression of inner ear hair cell markers and characteristics than delivery of MATH-1. Inhibition of HES1 and HES5 signaling further increased the atonal effect. Transfection of hWJCs with HATH1 DNA, HES1 siRNA, and HES5 siRNA displayed positive identification of key hair cell and support cell markers found in the cochlea, as well as a variety of cell shapes, sizes, and features not native to hair cells, suggesting the need for further examination of other cell types induced by HATH1 expression. In the first side-by-side evaluation of HATH1 and MATH-1 in human cells, substantial differences were observed, suggesting that the two atonal homologues may not be interchangeable in human cells, and artificial expression of HATH1 in hWJCs requires further study. In the future, this line of research may lead to engineered systems that would allow for evaluation of drug ototoxicity or potentially even direct therapeutic use.
authors.affiliation: 1Bioengineering Graduate Program, University of Kansas, Lawrence, Kansas.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Mellott
authors.affiliation: 2Department of Genetics, Stanford University, Stanford, California.
authors.forename: Keerthana
authors.initials: K
authors.lastname: Devarajan
authors.affiliation: 3Microscopy and Analytical Imaging Lab, University of Kansas, Lawrence, Kansas.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Shinogle
authors.affiliation: 3Microscopy and Analytical Imaging Lab, University of Kansas, Lawrence, Kansas.
authors.forename: David S
authors.initials: DS
authors.lastname: Moore
authors.affiliation: 4Department of Mathematics, University of Kansas, Lawrence, Kansas.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Talata
authors.affiliation: 1Bioengineering Graduate Program, University of Kansas, Lawrence, Kansas.|5Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Laurence
authors.affiliation: 1Bioengineering Graduate Program, University of Kansas, Lawrence, Kansas.|5Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas.
authors.forename: M Laird
authors.initials: ML
authors.lastname: Forrest
authors.affiliation: 6Department of Life Systems, Institute of Technology and Science, The University of Tokushima, Minami-Jyosanjima-cho, Tokushima, Japan.
authors.forename: Sumihare
authors.initials: S
authors.lastname: Noji
authors.affiliation: 7Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.affiliation: 1Bioengineering Graduate Program, University of Kansas, Lawrence, Kansas.|8Department of Otolaryngology, Head and Neck Surgery, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Hinrich
authors.initials: H
authors.lastname: Staecker
authors.affiliation: 1Bioengineering Graduate Program, University of Kansas, Lawrence, Kansas.|9Department of Chemical and Petroleum Engineering, University of Kansas, Lawrence, Kansas.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Detamore
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage; D000067470:Cellular Reprogramming Techniques / Q000379:methods*; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006199:Hair Cells, Auditory, Inner / Q000166:cytology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D000081412:Myosin VIIa; D009218:Myosins / Q000096:biosynthesis / Q000235:genetics; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013045:Species Specificity; D000072056:Transcription Factor HES-1; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005456:Fluorescent Dyes; D018398:Homeodomain Proteins; D000081412:Myosin VIIa; D009218:Myosins; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C500942:ATOH1 protein, human; C500943:Atoh1 protein, mouse; C073804:FM1 43; C000631455:MYO7A protein, human; C000631456:Myo7a protein, mouse; C077478:HES5 protein, human; C078493:HES1 protein, human