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Series GSE192735 Query DataSets for GSE192735
Status Public on Sep 15, 2022
Title Cross-lineage Potential of Ascl1 Uncovered by Comparing Diverse Reprogramming Regulatomes [RNA-seq II]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Direct reprogramming has revolutionized the fields of stem cell biology and regenerative medicine. Direct reprogramming makes it possible to interconvert somatic cell fates without intermediary pluripotency. Although studies have identified different transcription factor (TF) cocktails that can reprogram fibroblasts into different cell types, the common mechanisms governing how reprogramming cells undergo transcriptome and epigenome remodeling (i.e. regulatome remodeling) have not been investigated. Here, by characterizing early changes in the regulatome of three different types of direct reprogramming – induced neurons, induced hepatocytes, and induce cardiomyocytes – we identified two non-cocktail TFs, Tead4 and Atf7, that co-operate with reprogramming TFs to regulate target cell-type specific gene expression. Additionally, by identifying shared pro-cardiac features of iN and iCM reprogramming, we demonstrate Ascl1’s cross-lineage potential to induce highly efficient iCM reprogramming in a two-factor cocktail with Mef2c (A+M). Single-cell multi-omics showed that A+M reprogramming terminates in a more mature iCM phenotype than MGT. Finally, through ChIP-seq and RNA-seq, we find that Mef2c drives the shift in Ascl1 binding away from neuronal genes towards cardiac gene, guiding their co-operative epigenetic and transcription activities. These findings demonstrate the existence of common regulators of different direct reprogramming process and argue against the premise that TFs are lineage specific – the basic premise used to develop direct reprogramming approaches.
 
Overall design RNA-seq libraries of iN, IHep, and iCM were generated at day 3 post infection using the Roche KAPA Stranded mRNA-Seq kit
 
Contributor(s) Wang H, keepers B, Liu J, Qian L
Citation(s) 36206732
Submission date Dec 29, 2021
Last update date Dec 15, 2022
Contact name LI QIAN
E-mail(s) li_qian@med.unc.edu
Phone 919 9624982
Organization name UNC
Department Department of pathology
Lab Qian Lab
Street address 111 Mason Farm Road, MBRB
City Chapel Hill
ZIP/Postal code 27517
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (12)
GSM5764211 BAM_RNA_rep1
GSM5764212 BAM_RNA_rep2
GSM5764213 TETG_RNA_rep1
This SubSeries is part of SuperSeries:
GSE192788 Cross-lineage Potential of Ascl1 Uncovered by Comparing Diverse Reprogramming Regulatomes
Relations
BioProject PRJNA792992

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE192735_Tri_tpmMatrix_allSamples.csv.gz 1.9 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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