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Series GSE176206 Query DataSets for GSE176206
Status Public on Jun 10, 2022
Title Partial reprogramming restores youthful gene expression through transient suppression of cell identity
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Transient induction of pluripotent reprogramming factors has been reported to reverse some features of aging in mammalian cells and tissues. However, the impact of transient reprogramming on somatic cell identity programs and the necessity of individual pluripotency factors remain unknown. Here, we mapped trajectories of transient reprogramming in young and aged cells from multiple murine cell types using single cell transcriptomics to address these questions. We found that transient reprogramming restored youthful gene expression in adipogenic cells and mesenchymal stem cells but also temporarily suppressed somatic cell identity programs. We further screened Yamanaka Factor subsets and found that many combinations had an impact on aging gene expression and suppressed somatic identity, but that these effects were not tightly entangled. We also found that a transient reprogramming approach inspired by amphibian regeneration restored youthful gene expression in aged myogenic cells. Our results suggest that transient pluripotent reprogramming poses a neoplastic risk, but that restoration of youthful gene expression can be achieved with alternative strategies.
Overall design Mouse adipogenic cells and mesenchymal stem cells (MSCs) were treated with inducible OSKM reprogramming factors delivered by lentivirus for 3 days followed by a 3 day chase and subsequently profiled by single cell RNA-seq. MSCs were treated with barcoded lentiviral vectors carrying each of the OSKM factors separately. Cells from young (2-4 months old) and aged (20-30 months old) animals were used for all experiments. Myogenic cells from aged animals were treated with transient Msx1 expression on an inducible lentivirus for 3 days followed by a 3-4 day chase period. Pooled screens were performed with barcoded S, O, K, M viruses in MSCs.
Contributor(s) Kimmel JC
Citation(s) 35690067
Submission date Jun 05, 2021
Last update date Jun 16, 2022
Contact name Jacob Cameron Kimmel
Phone 3215361919
Organization name Calico Life Sciences, LLC
Department Computing
Street address 1170 Veterans Blvd
City South San Francisco
State/province CA
ZIP/Postal code 94080
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (18)
GSM5360083 Adipo_Young_SOKM
GSM5360084 Adipo_Young_Control
GSM5360085 Adipo_Aged_SOKM
BioProject PRJNA735380
SRA SRP322835

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Supplementary file Size Download File type/resource
GSE176206_adipo_screen.h5ad.gz 3.2 Gb (ftp)(http) H5AD
GSE176206_adipo_sokm.h5ad.gz 8.5 Gb (ftp)(http) H5AD
GSE176206_msc_screen.h5ad.gz 3.1 Gb (ftp)(http) H5AD
GSE176206_msc_sokm.h5ad.gz 4.9 Gb (ftp)(http) H5AD
GSE176206_myo_msx1.h5ad.gz 502.9 Mb (ftp)(http) H5AD
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