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Series GSE181800 Query DataSets for GSE181800
Status Public on May 06, 2022
Title Cellular identity loss occurring during both iPS cells generation and malignant transformation can be followed using the somatic markers Thy1 and Bcl11b [RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design R-BLTL and T-BLTL intermediates being more prone to reprogram / transform, we FACS-sorted R-BLTL/T-BLTL and R-BHTH/T-BHTH in their way to pluripotency or malignancy to identify new regulators. RNA-seq analyses were conducted on untreated MEFs alongside R-BLTL and T-BLTL (both Bcl11blow/thy1low), R-BHTH and T-BHTH (both Bcl11bhigh/thy1high) at 5 days of reprogramming or transformation and in iPS and transformed cells (TC).
Contributor(s) Lavial F, Huyghe A, Furlan G
Citation(s) 36075976
Submission date Aug 10, 2021
Last update date Oct 04, 2022
Contact name Fabrice Lavial
Organization name CRCL
Street address 28 rue Laennec
City Lyon
ZIP/Postal code 69008
Country France
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (10)
GSM5511554 MEF rep1 (RNA-seq)
GSM5511555 MEF rep2 (RNA-seq)
GSM5511556 R-BLTL (Reprogramming Intermediate Prone) rep1 (RNA-seq)
This SubSeries is part of SuperSeries:
GSE137050 The comparative roadmaps of reprogramming and transformation unveiled that cellular plasticity is broadly controlled by Bcl11b and Atoh8
BioProject PRJNA753494
SRA SRP331918

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Supplementary file Size Download File type/resource
GSE181800_model_fc.csv.gz 1.9 Mb (ftp)(http) CSV
GSE181800_normalized_count.csv.gz 1.3 Mb (ftp)(http) CSV
GSE181800_raw_count.csv.gz 661.5 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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