Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Analyses of iHC transcriptome profiles

ABSTRACT: Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. However, very little is known about the transcriptional regulators involved in HC fate determination and differentiation. In this paper, we show that expression of three HC lineage-specific transcription factors: Gfi1, Pou4f3 and Atoh1, can induce a direct commitment towards HC fate during in vitro embryonic stem cell (ESC) differentiation. Induced HCs (iHCs) express numerous HC-specific genes and exhibit polarized membrane protusions reminiscent of stereociliary bundles. The ability to obtain purified populations of iHCs by virtue of the Myo7:mVenus reporter line (iGPA-Myo7a:mVenus) allowed us to generate highly reproducible gene expression profiles for these cells, at various phases of their development (day 8 and day 12 of cell culture).

ORGANISM(S): Mus musculus

PROVIDER: GSE60352 | GEO | 2015/06/02

SECONDARY ACCESSION(S): PRJNA258081

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

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 | GSE181307 | GEO

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

2022-07-22 | GSE181310 | GEO

ATACseq, CutnRun and RNAseq data from Merkel cell and Touch dome epithelial progenitor cells, from wild type and Pou4f3-mutant epidermis

Project description:The role of POU4F3 in Merkel cell maturation, but not induction, is similar to its role in hair cells. This prompted us to investigate whether POU4F3 also regulates the accessibility of ATOH1 targets in a feed-forward manner during the maturation of Merkel cells. Our results suggest that, just as in hair cells, the pioneer factor activity of POU4F3 is also required for ATOH1 to correctly coordinate mechanosensory differentiation in Merkel cells.

2021-07-09 | GSE150388 | GEO

ATACseq, CutnRun and RNAseq data from sensory progenitors and hair cells, from wild type and Pou4f3-mutant cochlea

Project description:Hearing and balance are mediated in vertebrates by inner ear mechanosensory hair cells. Hair cell development, maturation and survival require POU4F3, a class IV POU domain transcription factor that is expressed in hair cells shortly after they start to differentiate. Here, we show that POU4F3 has pioneer factor activity, and is necessary to promote chromatin accessibility at approximately half of the distal regulatory elements that appear as hair cells differentiate. Pou4f3 expression in the inner ear is initiated by ATOH1, a bHLH transcription factor that is also necessary for hair cell differentiation and survival. We show that ATOH1 also binds a large number of POU4F3-dependent distal regulatory elements, suggesting a synergistic feed-forward model in which ATOH1 induces POU4F3, which then acts to promote ATOH1-dependent hair cell differentiation.

2021-07-09 | GSE150386 | GEO

Transcriptome-wide comparison of the impact of Atoh1 and miR-183 family on pluripotent stem cells and multipotent otic progenitors

Project description:Hair cells (HCs) are the mechanoreceptors responsible for hearing and balance in the inner ear. Multiple factors cause HC loss including aging, noise exposure and genetic predisposition. A barrier to hearing restoration after HC loss is the inability of mammalian auditory HCs to spontaneously regenerate. Multiple factors are shown to be crucial for HC development and represent good candidates for regenerative studies. Atoh1 is widely accepted to be necessary and contextually sufficient for driving HC fate. Furthermore, the miRNA-183 family is known to be expressed at the time of HC differentiation, and mutations in miR-96 (one member of the family) can cause deafness both in mouse and human. Our goal is to identify and compare the impact of Atoh1/miR-183 family alone and in combination on the transcriptome of two different developmental cell models; mouse embryonic stem cells (mESCs) and immortalized multipotent otic progenitors (iMOPs)

2017-07-01 | GSE81667 | GEO

Identification of intermediate transcriptome states and synergistic effects of Isl1 in Atoh1-mediated cochlear hair cell conversion

Project description:Ectopic expression of Atoh1 in non-sensory supporting cells (SCs) in mouse cochleae induces their conversion to hair cells (HCs) in vivo. cHCs in multiple intermediate states of the conversion process that most closely resembled neonatal differentiating HCs, but differed from the progenitors. We further identified 52 transcription factors that are differentially expressed in cHCs, SCs, and mature HCs and confirmed that Isl1 synergistically enhanced the efficiency of Atoh1-mediated HC conversion in cochlear explants. Our results demonstrate that direct HC conversion from SCs in vivo follows a different path from normal development and requires multiple factors for maximum efficiency and completion.

2018-07-23 | GSE85983 | GEO

Emx2 defines bidirectional polarity of neuromasts by changing hair-bundle orientation and not hair-cell positions

Project description:The bidirectional sensitivity of neuromasts to water flow in the zebrafish lateral line system is attributed to the opposite orientation of the hair bundles on top of sensory hair cells (HC) within a neuromast. After each HC precursor divides to form two nascent HCs, HCs of the same bundle orientation are positioned on one side of the neuromast, across from HCs with opposite bundle orientation. The transcription factor emx2 is expressed in only one of the sibling HCs. Loss or gain of function of emx2 in HCs causes unidirectional hair bundle orientation in neuromasts. It is not clear whether Emx2 is required specifically in establishing hair bundle orientation after HC formation or Emx2 has an earlier role in HC fate and/or positioning, which indirectly changes hair bundle orientation. A phenomenon, in which nascent sibling HCs exchange positions with each other, has been postulated to be the mechanism for HCs to acquire their designated positions within the neuromast. We asked whether Emx2 is involved in positional acquisition of HCs within the neuromast. Using live-imaging and our emx2 reporter we find that the HC rearrangement, redefined as two processes named Rock & Roll are required for HCs to acquire their positions. Although Emx2 regulates the duration of the Rock and the frequency of Roll of nascent HCs, it is not required for their positional acquisition. Instead, Emx2 regulates the morphology of nascent HCs, which facilitates the rearrangement process.

2021-01-19 | GSE152859 | GEO

Analyses of the individual and combinatorial transcriptional effects mediated by Atoh1, Pou4f3 and Gfi1 overexpression during embryoid body differentiation in vitro

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 | GSE136837 | GEO

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

2022-08-10 | GSE136836 | GEO

Single cell gene expression profile of adult cochlear explants over the course of hair cell regeneration stimulated by Atoh1 activation [DoxVehicleAtoh1]

Project description:Strategies to overcome irreversible cochlear hair cell (HC) damage and loss are of vital importance to develop a treatment for hearing loss. HC regeneration in adult cochlea relies on a two-phase process: 1) Reprogramming mature cochlear (SCs) to regain the properties of their younger selves; 2) Activating Atoh1, a gene responsible for HC fate-determining, in the reprogrammed adult SCs for HC regeneration. We have shown that, by transient co-activation of Myc and NICD (Notch1 intracellular domain), the adult mouse cochlea can be successfully reprogrammed to a relatively younger stage and regain progenitor capacity, with the regeneration of HCs following Atoh1 overexpression in vitro and in vivo. To identify molecules to reprogram mature cochlear SCs and HC regeneration, we utilized single-cell RNA sequencing and uncovered the pathways and their target genes underlying MYC/NICD-mediated reprogramming. We used an in-house adult cochlea explant culture system and carried out single-cell RNA sequencing to examine the gene expression profiles of cochlear explants from a transgenic mouse model, rtTa/tet-Myc/-tet-NICD, in response to Dox-induced MYC/NICD co-activation. We compared gene expression profiles between Atoh1 activation vs. MYC/NICD/Atoh1 co-activation.

2023-06-01 | GSE218325 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data