Current neuromodulation techniques such as optogenetics and deep-brain stimulation are transforming basic and translational neuroscience. These two neuro- modulation approaches are, however, invasive since surgical im...Current neuromodulation techniques such as optogenetics and deep-brain stimulation are transforming basic and translational neuroscience. These two neuro- modulation approaches are, however, invasive since surgical implantation of an optical fiber or wire electrode is required. Here, we have invented a non-invasive magnetogenetics that combines the genetic targeting of a mag- netoreceptor with remote magnetic stimulation. The noninvasive activation of neurons was achieved by neuronal expression of an exogenous magnetoreceptor, an iron-sulfur cluster assembly protein 1 （Iscal）. In HEK-293 cells and cultured hippocampal neurons expressing this magnetoreceptor, application of an external magnetic field resulted in membrane depolarization and calcium influx in a reproducible and reversible manner, as indicated by the ultrasensitive fluorescent calcium indicator GCaMP6s.Moreover, the magnetogenetic control of neuronal activity might be dependent on the direction of the magnetic field and exhibits on-response and off-response patterns for the external magnetic field applied. The activation of this magnetoreceptor can depolarize neurons and elicit trains of action potentials, which can be triggered repetitively with a remote magnetic field in whole-cell patch-clamp recording. In transgenic Caenorhabditis elegans expressing this magnetoreceptor in myo-3-specific muscle cells or mec-4- specific neurons, application of the external magnetic field triggered muscle contraction and withdrawal behavior of the worms, indicative of magnet-dependent activation of muscle cells and touch receptor neurons, respectively. The advantages of magnetogenetics over optogenetics are its exclusive non-invasive, deep penetration, long-term continuous dosing, unlimited accessibility, spatial uniformity and relative safety. Like optogenetics that has gone through decade-long improvements, magnetogenetics, with continuous modification and maturation, will reshape the current landscape of neuromodulation toolboxes and will have a broad range of applications to basic and translational neuroscience as well as other biological sciences. We envision a new age of magnetogenetics is coming.展开更多
Nanomaterials are increasingly used for biomedical applications; thus, it is important to understand their biological effects. Previous studies suggested that magnetic iron oxide nanoparticles （IONPs） have tissue-re...Nanomaterials are increasingly used for biomedical applications; thus, it is important to understand their biological effects. Previous studies suggested that magnetic iron oxide nanoparticles （IONPs） have tissue-repairing effects. In the present study, we explored cellular effects of IONPs in mesenchymal stem cells （MSCs） and identified the underlying molecular mechanisms. The results showed that our as-prepared IONPs were structurally stable in MSCs and promoted osteogenic differentiation of MSCs as whole particles. Moreover, at the molecular level, we compared the gene expression of MSCs with or without IONP exposure and showed that IONPs upregulated long noncoding RNA INZEB2, which is indispensable for maintaining osteogenesis by MSCs. Furthermore, overexpression of INZEB2 downregulated ZEB2, a factor necessary to repress BMP/Smad- dependent osteogenic transcription. We also demonstrated that the essential role of INZEB2 in osteogenic differentiation was ZEB2-dependent. In summary, we elucidated the molecular basis of IONPs＇ effects on MSCs; these findings may serve as a meaningful theoretical foundation for applications of stem cells to regenerative medicine.展开更多
Magnetoreception is a hallmark ability of animals for orientation and migration via sensing and utilizing geomagnetic fields.Magnetoreceptor(MagR) and cryptochromes(Cry) have recently been identified as the basis for ...Magnetoreception is a hallmark ability of animals for orientation and migration via sensing and utilizing geomagnetic fields.Magnetoreceptor(MagR) and cryptochromes(Cry) have recently been identified as the basis for magnetoreception in Drosophila.However,it has remained unknown whether MagR and Cry have conserved roles in diverse animals.Here we report the identification and expression of magr and cry genes in the fish medaka(Oryzias latipes).Cloning and sequencing identified a single magr gene,four cry genes and one cry-like gene in medaka.By sequence alignment,chromosomal synteny and gene structure analysis,medaka cry2 and magr were found to be the orthologs of human Cry2 and Magr,with cry1 aa and crylab being coorthologs of human Cry1.Therefore,magr and cry2 have remained as single copy genes,whereas cry1 has undergone two rounds of gene duplication in medaka.Interestingly,magr and cry genes were detected in various stages throughout embryogenesis and displayed ubiquitous expression in adult organs rather than specific or preferential expression in neural organs such as brain and eye.Importantly,magr knockdown by morpholino did not produce visible abnormality in developing embryos,pointing to the possibility of producing viable magr knockouts in medaka as a vertebrate model for magnet biology.展开更多
基金supported by Tsinghua-Peking Center for Life SciencesIDG/Mc Govern Foundationthe National Natural Science Foundation of China
文摘Current neuromodulation techniques such as optogenetics and deep-brain stimulation are transforming basic and translational neuroscience. These two neuro- modulation approaches are, however, invasive since surgical implantation of an optical fiber or wire electrode is required. Here, we have invented a non-invasive magnetogenetics that combines the genetic targeting of a mag- netoreceptor with remote magnetic stimulation. The noninvasive activation of neurons was achieved by neuronal expression of an exogenous magnetoreceptor, an iron-sulfur cluster assembly protein 1 （Iscal）. In HEK-293 cells and cultured hippocampal neurons expressing this magnetoreceptor, application of an external magnetic field resulted in membrane depolarization and calcium influx in a reproducible and reversible manner, as indicated by the ultrasensitive fluorescent calcium indicator GCaMP6s.Moreover, the magnetogenetic control of neuronal activity might be dependent on the direction of the magnetic field and exhibits on-response and off-response patterns for the external magnetic field applied. The activation of this magnetoreceptor can depolarize neurons and elicit trains of action potentials, which can be triggered repetitively with a remote magnetic field in whole-cell patch-clamp recording. In transgenic Caenorhabditis elegans expressing this magnetoreceptor in myo-3-specific muscle cells or mec-4- specific neurons, application of the external magnetic field triggered muscle contraction and withdrawal behavior of the worms, indicative of magnet-dependent activation of muscle cells and touch receptor neurons, respectively. The advantages of magnetogenetics over optogenetics are its exclusive non-invasive, deep penetration, long-term continuous dosing, unlimited accessibility, spatial uniformity and relative safety. Like optogenetics that has gone through decade-long improvements, magnetogenetics, with continuous modification and maturation, will reshape the current landscape of neuromodulation toolboxes and will have a broad range of applications to basic and translational neuroscience as well as other biological sciences. We envision a new age of magnetogenetics is coming.
文摘Nanomaterials are increasingly used for biomedical applications; thus, it is important to understand their biological effects. Previous studies suggested that magnetic iron oxide nanoparticles （IONPs） have tissue-repairing effects. In the present study, we explored cellular effects of IONPs in mesenchymal stem cells （MSCs） and identified the underlying molecular mechanisms. The results showed that our as-prepared IONPs were structurally stable in MSCs and promoted osteogenic differentiation of MSCs as whole particles. Moreover, at the molecular level, we compared the gene expression of MSCs with or without IONP exposure and showed that IONPs upregulated long noncoding RNA INZEB2, which is indispensable for maintaining osteogenesis by MSCs. Furthermore, overexpression of INZEB2 downregulated ZEB2, a factor necessary to repress BMP/Smad- dependent osteogenic transcription. We also demonstrated that the essential role of INZEB2 in osteogenic differentiation was ZEB2-dependent. In summary, we elucidated the molecular basis of IONPs＇ effects on MSCs; these findings may serve as a meaningful theoretical foundation for applications of stem cells to regenerative medicine.
基金supported by the National Research Foundation of Singapore(NRF-CRP7-2010-03)
文摘Magnetoreception is a hallmark ability of animals for orientation and migration via sensing and utilizing geomagnetic fields.Magnetoreceptor(MagR) and cryptochromes(Cry) have recently been identified as the basis for magnetoreception in Drosophila.However,it has remained unknown whether MagR and Cry have conserved roles in diverse animals.Here we report the identification and expression of magr and cry genes in the fish medaka(Oryzias latipes).Cloning and sequencing identified a single magr gene,four cry genes and one cry-like gene in medaka.By sequence alignment,chromosomal synteny and gene structure analysis,medaka cry2 and magr were found to be the orthologs of human Cry2 and Magr,with cry1 aa and crylab being coorthologs of human Cry1.Therefore,magr and cry2 have remained as single copy genes,whereas cry1 has undergone two rounds of gene duplication in medaka.Interestingly,magr and cry genes were detected in various stages throughout embryogenesis and displayed ubiquitous expression in adult organs rather than specific or preferential expression in neural organs such as brain and eye.Importantly,magr knockdown by morpholino did not produce visible abnormality in developing embryos,pointing to the possibility of producing viable magr knockouts in medaka as a vertebrate model for magnet biology.
