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Series GSE169519 Query DataSets for GSE169519
Status Public on May 04, 2023
Title Direct neuronal reprogramming by temporal identity factors
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors and shift cell fate output, but whether they can also reprogram the identity of terminally differentiated cells is unknown. To address this question, we designed a conditional gene expression system that allows rapid screening of potential reprogramming factors in mouse retinal glial cells combined with genetic lineage tracing. Using this assay, we found that co-expression of the early temporal identity transcription factors Ikzf1 and Ikzf4 is sufficient to directly convert Müller glial cells into cells that translocate to the outer nuclear layer (ONL), where photoreceptor cells normally reside. We name these “induced ONL (iONL)” cells. Using genetic lineage tracing, histological, immunohistochemical, and single-cell transcriptome and multiome analyses, we show that expression of Ikzf1/4 in Müller glia in vivo, without retinal injury, mostly generate iONL cells that share molecular characteristics with bipolar cells, although a fraction of them stain for Rxrg, a cone photoreceptor marker. Furthermore, we show that co-expression of Ikzf1 and Ikzf4 can reprogram mouse embryonic fibroblasts to induced neurons (iN) in culture by rapidly remodeling chromatin and activating a neuronal gene expression program. This work uncovers general neuronal reprogramming properties for temporal identity factors in terminally differentiated cells.
 
Overall design ScRNA-seq and joint cell scRNA/ATAC-seq analysis of reprogrammed Muller glia and RNA-seq/ATAC-seq analysis of reprogrammed MEFs
 
Contributor(s) Boudreau-Pinsonneault C, David LA, Lourenço Fernandes JA, Javed A, Fries M, Mattar P, Cayouette M
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Submission date Mar 24, 2021
Last update date May 23, 2023
Contact name Awais Javed
E-mail(s) awaisj14@gmail.com, awais.javed@ircm.qc.ca
Phone 5149875772
Organization name IRCM
Lab Michel Cayouette
Street address 110 Avenue des Pins
City Montreal
State/province Quebec
ZIP/Postal code H2W1R7
Country Canada
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (18)
GSM5208239 scRNA-seq - Control
GSM5208240 scRNA-seq - Ikzf1/4
GSM5208241 ATAC-seq 48hours BM rep1
Relations
BioProject PRJNA716964
SRA SRP311955

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
GSE169519_MEF_48h_BMIkzf14vsBM.txt.gz 957.1 Kb (ftp)(http) TXT
GSE169519_RAW.tar 2.2 Gb (http)(custom) TAR (of BED, BIGWIG, H5, LOOM, SF, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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