Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bcl11b and Atoh8 binding on chromatin in MEFs

ABSTRACT: Coordinated changes of cellular plasticity and cellular identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of cellular/molecular events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvoluted the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and revealed how the two processes intersect prior to bifurcate. This approach also led to identify the transcription factor (TF) Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multi-omics characterization of these intermediates led to unveil a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains rodent and human reprogramming but also cancer cell plasticity and neuron transdifferentiation. Mechanistically, we found that the TF Atoh8 restrains cellular plasticity, independently of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.

ORGANISM(S): Mus musculus

PROVIDER: GSE181196 | GEO | 2022/05/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Chromatin accessibility after 5 days of reprogramming and transformation

Project description:Coordinated changes of cellular plasticity and cellular identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of cellular/molecular events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvoluted the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and revealed how the two processes intersect prior to bifurcate. This approach also led to identify the transcription factor (TF) Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multi-omics characterization of these intermediates led to unveil a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains rodent and human reprogramming but also cancer cell plasticity and neuron transdifferentiation. Mechanistically, we found that the TF Atoh8 restrains cellular plasticity, independently of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.

2022-05-06 | GSE181796 | GEO

Cellular identity loss occurring during both iPS cells generation and malignant transformation can be followed using the somatic markers Thy1 and Bcl11b [scRNA-seq]

2022-05-06 | GSE181451 | GEO

The comparative roadmaps of reprogramming and transformation unveiled that cellular plasticity is broadly controlled by Bcl11b and Atoh8

Project description:Coordinated changes of cellular plasticity and cellular identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of cellular/molecular events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvoluted the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and revealed how the two processes intersect prior to bifurcate. This approach also led to identify the transcription factor (TF) Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming & transformation. Multi-omics characterization of these intermediates led to unveil a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains rodent and human reprogramming but also cancer cell plasticity and neuron transdifferentiation. Mechanistically, we found that the TF Atoh8 restrains cellular plasticity, independently of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.

2022-05-06 | GSE137050 | GEO

Cellular identity loss occurring during both iPS cells generation and malignant transformation can be followed using the somatic markers Thy1 and Bcl11b [RNA-seq]

2022-05-06 | GSE181800 | GEO

Cellular identity loss occurring during both iPS cells generation and malignant transformation can be followed using the somatic markers Thy1 and Bcl11b (ATAC-seq)

2022-05-06 | GSE181799 | GEO

Coordinate Enhancer Reprogramming by GATA3 and AP1 Promotes Phenotypic Plasticity to Achieve Breast Cancer Endocrine Resistance

Project description:Phenotypic plasticity has emerged as an important mechanism of therapy resistance in cancers, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model for endocrine resistance, we show that hormone resistance is associated with enhanced phenotypic plasticity, indicated by a general downregulation of luminal/epithelial differentiation markers and upregulation of basal/mesenchymal invasive markers. Our extensive omics studies, including GRO-seq on enhancer landscapes, demonstrate that the global enhancer gain/loss reprogramming driven by the differential interactions between ER-alpha and other oncogenic transcription factors (TFs), predominantly GATA3 and AP1, profoundly alters breast cancer transcriptional programs. Our functional studies in multiple biological systems support a coordinate role of GATA3 and AP1 in enhancer reprogramming that drives phenotypic plasticity to achieve endocrine resistance or cancer invasive progression. Thus, changes in TF-TF and TF-enhancer interactions can lead to genome-wide enhancer reprogramming, resulting in transcriptional dysregulations that promote plasticity and cancer therapy-resistance progression

2019-05-24 | MSV000083857 | MassIVE

The comparative roadmaps of reprogramming and transformation unveiled that cellular plasticity is broadly controlled by Bcl11b and Atoh8

Project description:The comparative roadmaps of reprogramming and transformation unveiled that cellular plasticity is broadly controlled by Bcl11b and Atoh8

| PRJNA564325 | ENA

Enhancer reprogramming driven by high-order assemblies of transcription factors promotes phenotypic plasticity and breast cancer endocrine resistance [RNA-Seq]

Project description:Cellular plasticity has emerged as an important mechanism of therapy resistance in cancers, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model for endocrine resistance, we show that hormone resistance is associated with enhanced cellular plasticity, indicated by a general downregulation of luminal/epithelial differentiation markers and upregulation of basal/mesenchymal invasive markers. Our extensive omics studies including GRO-seq on enhancer landscapes demonstrate that the global enhancer gain/loss reprogramming driven by the differential interactions between ERα and other oncogenic transcription factors (TFs), predominantly GATA3 and AP1, profoundly alter breast cancer transcriptional programs. Our functional studies in various biological systems support a coordinated role of GATA3 and AP1-mediated enhancer reprogramming in driving cellular plasticity to achieve endocrine resistance or cancer invasive progression. Thus, changes in TF-TF and TF-enhancer interactions can lead to genome-wide enhancer reprogramming, resulting in transcriptional dysregulations that promote plasticity and cancer therapy-resistance progression.

2020-05-18 | GSE128458 | GEO