title: Transcriptome transfer produces a predictable cellular phenotype.
abstract: Cellular phenotype is the conglomerate of multiple cellular processes involving gene and protein expression that result in the elaboration of a cell's particular morphology and function. It has been thought that differentiated postmitotic cells have their genomes hard wired, with little ability for phenotypic plasticity. Here we show that transfer of the transcriptome from differentiated rat astrocytes into a nondividing differentiated rat neuron resulted in the conversion of the neuron into a functional astrocyte-like cell in a time-dependent manner. This single-cell study permits high resolution of molecular and functional components that underlie phenotype identity. The RNA population from astrocytes contains RNAs in the appropriate relative abundances that give rise to regulatory RNAs and translated proteins that enable astrocyte identity. When transferred into the postmitotic neuron, the astrocyte RNA population converts 44% of the neuronal host cells into the destination astrocyte-like phenotype. In support of this observation, quantitative measures of cellular morphology, single-cell PCR, single-cell microarray, and single-cell functional analyses have been performed. The host-cell phenotypic changes develop over many weeks and are persistent. We call this process of RNA-induced phenotype changes, transcriptome-induced phenotype remodeling.
authors.affiliation: Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jai-Yoon
authors.initials: JY
authors.lastname: Sul
authors.forename: Chia-wen K
authors.initials: CW
authors.lastname: Wu
authors.forename: Fanyi
authors.initials: F
authors.lastname: Zeng
authors.forename: Jeanine
authors.initials: J
authors.lastname: Jochems
authors.forename: Miler T
authors.initials: MT
authors.lastname: Lee
authors.forename: Tae Kyung
authors.initials: TK
authors.lastname: Kim
authors.forename: Tiina
authors.initials: T
authors.lastname: Peritz
authors.forename: Peter
authors.initials: P
authors.lastname: Buckley
authors.forename: David J
authors.initials: DJ
authors.lastname: Cappelleri
authors.forename: Margaret
authors.initials: M
authors.lastname: Maronski
authors.forename: Minsun
authors.initials: M
authors.lastname: Kim
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.forename: David
authors.initials: D
authors.lastname: Meaney
authors.forename: Junhyong
authors.initials: J
authors.lastname: Kim
authors.forename: James
authors.initials: J
authors.lastname: Eberwine
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014162:Transfection; D014466:Ultraviolet Rays
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger