Abstract：
:Generating mammalian cells with desired mitochondrial DNA (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-nuclear DNA (nDNA) combinations by transferring isolated mitochondria from mouse or human cells into primary or immortal mtDNA-deficient (ρ0) cells. Stable isolated mitochondrial recipient (SIMR) cells isolated in restrictive media permanently retain donor mtDNA and reacquire respiration. However, SIMR fibroblasts maintain a ρ0-like cell metabolome and transcriptome despite growth in restrictive media. We reprogrammed 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, after reprogramming and differentiation, SIMR fibroblasts molecularly and phenotypically resemble unmanipulated 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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Patananan AN,Sercel AJ,Wu TH,Ahsan FM,Torres A Jr,Kennedy SAL,Vandiver A,Collier AJ,Mehrabi A,Van Lew J,Zakin L,Rodriguez N,Sixto M,Tadros W,Lazar A,Sieling PA,Nguyen TL,Dawson ER,Braas D,Golovato J,Cisneros L,Vdoi
10.1016/j.celrep.2020.108562subject
Has Abstractpub_date
2020-12-29 00:00:00pages
108562issue
13issn
2211-1247pii
S2211-1247(20)31551-5journal_volume
33pub_type
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