A single-cell level comparison of human inner ear organoids with the human cochlea and vestibular organs

Valk, Wouter H. van der; Beelen, Edward S.A. van; Steinhart, Matthew R.; Nist-Lund, Carl; Osorio, Daniel; Groot, John C.M.J. de; Sun, Liang; Benthem, Peter Paul G. van; Koehler, Karl R.; Locher, Heiko

doi:10.1016/j.celrep.2023.112623

Cited by 19 publications

(12 citation statements)

References 131 publications

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“…In this study, a total of 34 genes with pathogenic, likely pathogenic, or possible pathogenic variants were defined as novel AN genes (Supplementary Table 4). The expression analysis of these novel AN genes was performed using the single-cell sequencing data of the human cochlea published by van der (van der Valk et al 2023 ). A comparative heatmap of the expression between 9.2-week-old infants (cochlea not fully differentiated) and adult human cochlea at the single-cell level was presented in Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The expression sites of the AN new genes were analyzed using single-cell sequencing data published by van der (van der Valk et al 2023 ) and Philippe Jean (Jean et al 2023 ). All the data mentioned were publicly available and were analyzed online using gGAR: Gene Expression Analysis Resource portal for community-driven, multi-omic data exploration.…”

Section: Methodsmentioning

confidence: 99%

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Clinical and genetic architecture of a large cohort with auditory neuropathy

Wang,

Guan,

et al. 2024

Hum. Genet.

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Auditory neuropathy (AN) is a unique type of language developmental disorder, with no precise rate of genetic contribution that has been deciphered in a large cohort. In a retrospective cohort of 311 patients with AN, pathogenic and likely pathogenic variants of 23 genes were identified in 98 patients (31.5% in 311 patients), and 14 genes were mutated in two or more patients. Among subgroups of patients with AN, the prevalence of pathogenic and likely pathogenic variants was 54.4% and 56.2% in trios and families, while 22.9% in the cases with proband-only; 45.7% and 25.6% in the infant and non-infant group; and 33.7% and 0% in the bilateral and unilateral AN cases. Most of the OTOF gene (96.6%, 28/29) could only be identified in the infant group, while the AIFM1 gene could only be identified in the non-infant group; other genes such as ATP1A3 and OPA1 were identified in both infant and non-infant groups. In conclusion, genes distribution of AN, with the most common genes being OTOF and AIFM1, is totally different from other sensorineural hearing loss. The subgroups with different onset ages showed different genetic spectrums, so did bilateral and unilateral groups and sporadic and familial or trio groups.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Clinical and genetic architecture of a large cohort with auditory neuropathy

Wang,

Guan,

et al. 2024

Hum. Genet.

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“…76 More recently, single-cell transcriptomic evaluations of organoids from human pluripotent stem cells support the general notion that organoid HCLCs default to a vestibular like fate. 74, 75 Even so, at least one report has shown evidence of both vestibular and cochlear HC fates with only slight modifications to the original Koehler protocol 77 and modulations of HH and WNT signaling were deemed sufficient to tip the balance towards cochlear cell fates. 24 Using scRNA-seq, we profiled a total of 3,029 HCLCs and in an unbiased clustering approach we determined that a significant number of HCLCs acquired a transcriptional signature reminiscent of auditory HCs.…”

Section: Discussionmentioning

confidence: 99%

Mapping the developmental potential of mouse inner ear organoids at single-cell resolution

Waldhaus,

Jiang,

Liu

et al. 2023

Preprint

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SummaryInner ear organoids recapitulate development and are intended to generate cell types of the otic lineage for applications such as basic science research and cell replacement strategies. Here, we use single-cell sequencing to study the cellular heterogeneity of late-stage mouse inner ear organoid sensory epithelia, which we validated by comparison with data sets of the mouse cochlea and vestibular epithelia. We resolved supporting cell sub-types, cochlear like hair cells, and vestibular Type I and Type II like hair cells. While cochlear like hair cells aligned best with an outer hair cell trajectory, vestibular like hair cells followed developmental trajectories similar toin vivoprograms branching into Type II and then Type I extrastriolar hair cells. These results highlight the transcriptional accuracy of the organoid developmental program but will also inform future strategies to improve synaptic connectivity and regional specification.

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“…By comparing single-cell profiling of IEOs, human fetal inner ear and adult vestibular epithelia, as well as by histological comparison, these studies established that in vitro differentiation follows similar timing and dynamics as in vivo. Cells differentiated in IEOs for 50–70 days match marker expression and maturity of weeks 10–12 human development [ 14 , 17 ]. Further differentiation in culture until days 150–200 brings the maturity of the culture closer to weeks 18–20 of fetal inner ear development, when functionality starts [ 12 ].…”

Section: Pluripotent Stem Cell–derived Inner Ear Organoids (Ieos)mentioning

confidence: 99%

“…The corroboration that in vitro differentiation recapitulates early human organ development and that genes associated with hearing loss are expressed in IEOs [ 14 , 16 , 17 ] has demonstrated the possibility for the use of these models to study defects caused by gene mutations, in particular for monogenic forms of hereditary deafness. The relevant literature for this approach has recently been reviewed [ 3 ].…”

Section: Modeling Developmental Defectsmentioning

confidence: 99%

Inner Ear Organoids: Strengths and Limitations

Pianigiani,

Roccio

2024

JARO

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Inner ear organoids derived from differentiation of human pluripotent stem cells have recently gained momentum as tools to study inner ear development and developmental defects. An additional exciting aspect about this technology is represented by its translational potential, specifically, the use of organoids to validate therapeutics for hearing and balance restoration on human/patient-specific cells. This latter aspect will be briefly discussed here including opportunities and current limitations.

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A single-cell level comparison of human inner ear organoids with the human cochlea and vestibular organs

Cited by 19 publications

References 131 publications

Clinical and genetic architecture of a large cohort with auditory neuropathy

Clinical and genetic architecture of a large cohort with auditory neuropathy

Mapping the developmental potential of mouse inner ear organoids at single-cell resolution

Inner Ear Organoids: Strengths and Limitations

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