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Series GSE115871 Query DataSets for GSE115871
Status Public on Dec 29, 2020
Title Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Generating mammalian cells with desired mtDNA sequences is enabling for studies of mitochondria, disease modeling, and potential regenerative therapies. MitoPunch, a high-throughput mitochondrial transfer device, produces cells with specific mtDNA-nDNA combinations by transferring isolated mitochondria from mouse or human cells into primary or immortal mtDNA-deficient (p0) cells. Stable isolated mitochondrial recipient (SIMR) cells isolated in restrictive media permanently retain donor mtDNA and reacquire respiration. However, SIMR fibroblasts maintain a p0-like cell metabolome and transcriptome despite growth in restrictive media. We reprogram non-immortal SIMR fibroblasts into induced pluripotent stem cells (iPSCs) with subsequent differentiation into diverse functional cell types, including mesenchymal stem cells (MSCs), adipocytes, osteoblasts, and chondrocytes. Remarkably, following reprogramming and differentiation, SIMR fibroblasts molecularly and phenotypically resemble un-manipulated control fibroblasts carried through the same protocol. Thus, our MitoPunch ‘pipeline’ enables the production of SIMR cells with unique mtDNA-nDNA combinations for additional studies and applications in multiple cell types.
Overall design Total ribo-depleted bulk RNA-sequencing of mtDNA depleted (p0) BJ human neonatal foreskin fibroblasts transferred HEK 293 DsRed mitochondria (n = 3) or human peripheral blood mononuclear cell (LP351 PBMC) mitochondria (n = 3), compared to wildtype (BJ, n = 3) and mtDNA depleted (BJ p0, n = 3) fibroblasts. Transferred BJ fibroblasts were reprogrammed into iPSC (n = 2 of three isolated clones each, 6 total) and each clone differentiated into MSC (n = 2 of each matched clone, 6 total) for functional assesment. Reprogramming and differentiations were compared to wildtype BJ fibroblast generation of iPSCs (n = 3) and MSCs (n = 3) (n = 60 total samples).
Contributor(s) Ahsan FM, Patananan AN, Sercel AJ, Wu T, Teitell MA
Citation(s) 33378680
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 CA185189 (PQD5) Mass Profiling Melanoma Responses to Improve Therapy Choices and Prognosis UNIVERSITY OF CALIFORNIA LOS ANGELES MICHAEL A TEITELL
R01 GM114188 Reverse Mitochondrial Genetics Enabled by Blast UNIVERSITY OF CALIFORNIA LOS ANGELES MICHAEL A TEITELL
R01 GM114188 Reverse Mitochondrial Genetics Enabled by Blast UNIVERSITY OF CALIFORNIA LOS ANGELES Pei-Yu Chiou
R21 EB014456 Microfluidics-Integrated Photothermal Nanoblade for High-Throughput Large Cargo D UNIVERSITY OF CALIFORNIA LOS ANGELES Pei-Yu Chiou
Submission date Jun 15, 2018
Last update date Mar 10, 2021
Contact name Fasih Mubtasim Ahsan
Organization name Massachusetts General Hospital
Department Center for Genomic Medicine
Lab Soukas Lab
Street address 185 Cambridge Street, CPZN 6500
City Boston
State/province MA
ZIP/Postal code 02114
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (60)
GSM3192197 BJ Rho Null Fibs; b8a9e771-5e64-4973-a459-f2de0182d439
GSM3192198 BJ Rho Null Fibs; 255d874b-6966-4235-b809-d26a97fc4b52
GSM3192199 BJ Rho Null Fibs; 73c987bf-fdd2-4674-a3c5-3352c8f7e96a
BioProject PRJNA476350
SRA SRP150642

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
GSE115871_GEO_rawcountmatrix.csv.gz 5.9 Mb (ftp)(http) CSV
GSE115871_GEO_samplemetadata.csv.gz 1.8 Kb (ftp)(http) CSV
GSE115871_RAW.tar 198.6 Mb (http)(custom) TAR (of TXT)
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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