title: Bioinspired nanocomplex for spatiotemporal imaging of sequential mRNA expression in differentiating neural stem cells.
abstract: Messenger RNA plays a pivotal role in regulating cellular activities. The expression dynamics of specific mRNA contains substantial information on the intracellular milieu. Unlike the imaging of stationary mRNAs, real-time intracellular imaging of the dynamics of mRNA expression is of great value for investigating mRNA biology and exploring specific cellular cascades. In addition to advanced imaging methods, timely extracellular stimulation is another key factor in regulating the mRNA expression repertoire. The integration of effective stimulation and imaging into a single robust system would significantly improve stimulation efficiency and imaging accuracy, producing fewer unwanted artifacts. In this study, we developed a multifunctional nanocomplex to enable self-activating and spatiotemporal imaging of the dynamics of mRNA sequential expression during the neural stem cell differentiation process. This nanocomplex showed improved enzymatic stability, fast recognition kinetics, and high specificity. With a mechanism regulated by endogenous cell machinery, this nanocomplex realized the successive stimulating motif release and the dynamic imaging of chronological mRNA expression during neural stem cell differentiation without the use of transgenetic manipulation. The dynamic imaging montage of mRNA expression ultimately facilitated genetic heterogeneity analysis. In vivo lateral ventricle injection of this nanocomplex enabled endogenous neural stem cell activation and labeling at their specific differentiation stages. This nanocomplex is highly amenable as an alternative tool to explore the dynamics of intricate mRNA activities in various physiological and pathological conditions.
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Ruili
authors.initials: R
authors.lastname: Zhang
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Wang
authors.forename: He-Fang
authors.initials: HF
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Fu
authors.initials: F
authors.lastname: Wang
authors.forename: Weitao
authors.initials: W
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D040761:Biomimetic Materials; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D049329:Nanostructures; D058953:Neural Stem Cells / Q000166:cytology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger
keywords: drug delivery; gold nanoparticle; imaging; mRNA; neural stem cell