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Single cell RNA-seq analysis of hair cell regeneration in the mammalian vestibular system and its potentiation by Atoh1

ABSTRACT: Single cell RNA-seq analysis of hair cell regeneration in the mammalian vestibular system and its potentiation by Atoh1

PROVIDER: PRJNA525021 | ENA |

REPOSITORIES: ENA

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RNA-seq analysis of hair cell regeneration in the mammalian vestibular system and its potentiation by Atoh1

Project description:RNA-seq analysis of hair cell regeneration in the mammalian vestibular system and its potentiation by Atoh1

| PRJNA506200 | ENA

Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1

Project description:The mammalian cochlea loses its ability to regenerate new hair cells prior to the onset of hearing. In contrast, the adult vestibular system can produce new hair cells in response to damage, or by reprogramming of supporting cells with the hair cell transcription factor Atoh1. We used RNA-seq and ATAC-seq to probe the transcriptional and epigenetic responses of utricle supporting cells to damage and Atoh1 transduction. We show that the improved regenerative response of the utricle correlates with a more accessible chromatin structure in utricle supporting cells compared to their cochlear counterparts. We also provide evidence that Atoh1 transduction of supporting cells is able to promote increased transcriptional accessibility of some hair cell genes. Our study offers a possible explanation for regenerative differences between sensory organs of the inner ear, but shows that additional factors to Atoh1 may be required for optimal reprogramming of hair cell fate.

2019-04-30 | GSE121610 | GEO

RNA-seq analysis of hair cell regeneration in the mammalian vestibular system and its potentiation by Atoh1

Project description:We used RNA-seq to probe the transcriptional and epigenetic responses of utricle supporting cells to damage and Atoh1 transduction.

2019-05-07 | GSE122732 | GEO

Single cell RNA-seq analysis of hair cell regeneration in the mammalian vestibular system and its potentiation by Atoh1

Project description:We used single cell RNA-seq to probe the transcriptional responses of utricle supporting cells to damage and Atoh1 transduction.

2019-05-20 | GSE127683 | GEO

Regenerating hair cells in human vestibular sensory epithelia

Project description:To investigate alterations in gene expression after Ad2-ATOH1-GFP transduction of human supporting cells, we measured transcriptome changes by RNA-seq. We compared gentamicin-treated tissue (to kill the hair cells) transduced with Ad2-ATOH1-GFP (to promote hair cell production) cultured for 5 days, versus control tissues only treated with gentamicin (cultured for 2 days, 8 days and 14-18 days).

2018-07-16 | GSE109320 | GEO

Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1

Project description:Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1

| PRJNA497870 | ENA

Characterization of the transcriptomes of Atoh1-induced hair cells in the mouse cochlea

Project description:Mammalian cochlea hair cells can be regenerated from the adjacent supporting cells in many ways, however, the newly hair cells are immature and without hearing function almost. The expression of Atoh1 is an important maker of the appearance of newly hair cells, many approaches of inner ear hair cells’ regeneration are concerned with the transcription factor Atoh1. However, most new HCs are immature HCs, and they do not have the function of mature HCs and eventually die a few weeks after regeneration. Thus promoting the maturation and survival of new HCs is the primary focus of HC regeneration field. We used RNA-Seq analysis to compare the differences between the transcriptomes of Atoh1 overexpression-induced new HCs and the original HCs, and to define the factors that might help to promote the maturation and survival of new HCs.

2019-04-10 | GSE129533 | GEO

Analyses of the Atoh1, Pou4f3 and Gfi1 genome binding profile during hair cell and neuronal differentiation

Project description:To gain new insights into the genetic networks regulating hair cell development, we developed a new transcriptional programming strategy to promote in vitro hair cell differentiation, starting from mouse embryonic stem cells (mESCs). In vivo, Atoh1 is the only transcription factor (TF) known to be necessary and sufficient for HC differentiation, but in vitro its overexpression induces neuronal rather than hair cell differentiation. We discovered that Atoh1 expression combined with two other TFs (Pou4f3, Gfi1) resulted in efficient hair cell generation. This work offers a new paradigm to understand the molecular mechanisms governing transcription factor specificity. For example, how do Pou4f3-Gfi1 modulate Atoh1 activity to orchestrate a HC differentiation program? To address this question, we have engineered several mESCs lines containing Atoh1, Gfi1 and/or Pou4f3 in a doxycycline-inducible locus to allow a controllable overexpression of every combination of these 3 transcriptional factors either using a polycistronic approach (mESCs lines: iG+A, iG+P, iP+A and iGPA) or by promoting their individual overexpression (mESCs lines: iAtoh1, iGfi1 and iPou4f3). These findings highlight the diversity of mechanisms by which one TF can redirect the activity of another to enable combinatorial control of cell identity.

2022-08-10 | GSE136836 | GEO

Three distinct Atoh1 enhancers cooperate for sound receptor hair cell development [ATAC-seq]

Project description:Cochlear hair cells (HCs) in the inner ear are responsible for sound detection. For HC fate specification, the master transcription factor Atoh1 is both necessary and sufficient. Atoh1 expression is dynamic and tightly regulated during development, but the cis-regulatory elements mediating this regulation remain unresolved. Unexpectedly, we found that deleting the only recognized Atoh1 enhancer, defined here as Eh1, failed to impair HC development. By using ATAC-seq (assay for transposase-accessible chromatin with high-throughput sequencing), we discovered two additional Atoh1 enhancers: Eh2 and Eh3. Notably, Eh2 deletion was sufficient for impairing HC development, and concurrent deletion of Eh1 and Eh2 or all three enhancers resulted in nearly complete absence of HCs. Lastly, we showed that Atoh1 binds to all three enhancers, consistent with its autoregulatory function. Our findings reveal that the cooperative action of three distinct enhancers underpins effective Atoh1 regulation during HC development, indicating potential therapeutic approaches for HC regeneration.

2022-07-22 | GSE181310 | GEO

Three distinct Atoh1 enhancers cooperate for sound receptor hair cell development [CUT&RUN]

2022-07-22 | GSE181307 | GEO

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