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Article: An integrated microfluidic bubble pocket for long-term perfused three-dimensional intestine-on-a-chip model.

Lee, Kang Kug Paul / Matsu-Ura, Toru / Rosselot, Andrew E / Broda, Taylor R / Wells, James M / Hong, Christian I

Biomicrofluidics

2021 Volume 15, Issue 1, Page(s) 14110

Abstract: Perfused three-dimensional (3D) cultures enable long- ... ...

Abstract	Perfused three-dimensional (3D) cultures enable long-term
Language	English
Publishing date	2021-02-17
Publishing country	United States
Document type	Journal Article
ISSN	1932-1058
ISSN	1932-1058
DOI	10.1063/5.0036527
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Article ; Online: WNT Takes Two to Tango: Molecular Links between the Circadian Clock and the Cell Cycle in Adult Stem Cells.

Matsu-Ura, Toru / Moore, Sean R / Hong, Christian I

Journal of biological rhythms

2017 Volume 33, Issue 1, Page(s) 5–14

Abstract: Like two dancers, the circadian clock and cell cycle are biological oscillators engaged in bidirectional communication, resulting in circadian clock-gated cell division cycles in species ranging from cyanobacteria to mammals. The identified mechanisms ... ...

Abstract	Like two dancers, the circadian clock and cell cycle are biological oscillators engaged in bidirectional communication, resulting in circadian clock-gated cell division cycles in species ranging from cyanobacteria to mammals. The identified mechanisms for this phenomenon have expanded beyond intracellular molecular coupling components to include intercellular connections. However, detailed molecular mechanisms, dynamics, and physiological functions of the circadian clock and cell cycle as coupled oscillators remain largely unknown. In this review, we discuss current understanding of this connection in light of recent findings that have uncovered intercellular coupling between the circadian clock in Paneth cells and the cell cycle in intestinal stem cells via WNT signaling. This extends the impact of circadian rhythms regulating the timing of cell divisions beyond the intracellular domain of homogenous cell populations into dynamic, multicellular systems. In-depth understanding of the molecular links and dynamics of these two oscillators will identify potential targets and temporal regimens for effective chronotherapy.
MeSH term(s)	Adult Stem Cells/metabolism ; Adult Stem Cells/physiology ; Animals ; Cell Cycle/physiology ; Circadian Clocks/physiology ; Circadian Rhythm/physiology ; Humans ; Wnt Proteins/metabolism ; Wnt Signaling Pathway/physiology
Chemical Substances	Wnt Proteins
Language	English
Publishing date	2017-12-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	896387-3
ISSN	1552-4531 ; 0748-7304
ISSN (online)	1552-4531
ISSN	0748-7304
DOI	10.1177/0748730417745913
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Article ; Online: Inositol 1,4,5-Trisphosphate Receptor Type 3 Regulates Neuronal Growth Cone Sensitivity to Guidance Signals.

Chan, Carmen / Ooashi, Noriko / Akiyama, Hiroki / Fukuda, Tetsuko / Inoue, Mariko / Matsu-Ura, Toru / Shimogori, Tomomi / Mikoshiba, Katsuhiko / Kamiguchi, Hiroyuki

iScience

2020 Volume 23, Issue 3, Page(s) 100963

Abstract: During neurodevelopment, the growth cone deciphers directional information from extracellular guidance cues presented as shallow concentration gradients via signal amplification. However, it remains unclear how the growth cone controls this amplification ...

Abstract	During neurodevelopment, the growth cone deciphers directional information from extracellular guidance cues presented as shallow concentration gradients via signal amplification. However, it remains unclear how the growth cone controls this amplification process during its navigation through an environment in which basal cue concentrations vary widely. Here, we identified inositol 1,4,5-trisphosphate (IP
Language	English
Publishing date	2020-03-05
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2020.100963
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Article: Efficient gene editing in

Matsu-Ura, Toru / Baek, Mokryun / Kwon, Jungin / Hong, Christian

Fungal biology and biotechnology

2015 Volume 2, Page(s) 4

Abstract: Background: Efficient gene editing is a critical tool for investigating molecular mechanisms of cellular processes and engineering organisms for numerous purposes ranging from biotechnology to medicine. Recently developed RNA-guided CRISPR/Cas9 ... ...

Abstract	Background: Efficient gene editing is a critical tool for investigating molecular mechanisms of cellular processes and engineering organisms for numerous purposes ranging from biotechnology to medicine. Recently developed RNA-guided CRISPR/Cas9 technology has been used for efficient gene editing in various organisms, but has not been tested in a model filamentous fungus, Findings: In this report, we demonstrate efficient gene replacement in a model filamentous fungus, Conclusion: CRISPR/Cas9 system works efficiently in
Language	English
Publishing date	2015-07-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2806612-1
ISSN	2054-3085
ISSN	2054-3085
DOI	10.1186/s40694-015-0015-1
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Article ; Online: Dual-FRET imaging of IP

Matsu-Ura, Toru / Shirakawa, Hideki / Suzuki, Kenichi G N / Miyamoto, Akitoshi / Sugiura, Kotomi / Michikawa, Takayuki / Kusumi, Akihiro / Mikoshiba, Katsuhiko

Scientific reports

2019 Volume 9, Issue 1, Page(s) 4829

Abstract: In most species, fertilization induces ... ...

Abstract	In most species, fertilization induces Ca
MeSH term(s)	Animals ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Calcium/metabolism ; Calcium Signaling/physiology ; Cations, Divalent/metabolism ; Female ; Fertilization/physiology ; Fluorescence Resonance Energy Transfer ; Fluorescent Dyes/chemistry ; Genes, Reporter/genetics ; HeLa Cells ; Humans ; Inositol 1,4,5-Trisphosphate/metabolism ; Intravital Microscopy ; Luminescent Proteins/chemistry ; Luminescent Proteins/genetics ; Male ; Mice ; Microinjections ; Microscopy, Fluorescence ; Sf9 Cells ; Sperm Injections, Intracytoplasmic ; Spodoptera ; Type C Phospholipases/metabolism ; Zygote/metabolism
Chemical Substances	Bacterial Proteins ; Cations, Divalent ; Fluorescent Dyes ; Luminescent Proteins ; yellow fluorescent protein, Bacteria ; Inositol 1,4,5-Trisphosphate (85166-31-0) ; Type C Phospholipases (EC 3.1.4.-) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2019-03-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-40931-w
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Article ; Online: Inositol 1,4,5-Trisphosphate Receptor Type 3 Regulates Neuronal Growth Cone Sensitivity to Guidance Signals

Carmen Chan / Noriko Ooashi / Hiroki Akiyama / Tetsuko Fukuda / Mariko Inoue / Toru Matsu-ura / Tomomi Shimogori / Katsuhiko Mikoshiba / Hiroyuki Kamiguchi

iScience, Vol 23, Iss 3, Pp - (2020)

2020

Abstract: Summary: During neurodevelopment, the growth cone deciphers directional information from extracellular guidance cues presented as shallow concentration gradients via signal amplification. However, it remains unclear how the growth cone controls this ... ...

Abstract	Summary: During neurodevelopment, the growth cone deciphers directional information from extracellular guidance cues presented as shallow concentration gradients via signal amplification. However, it remains unclear how the growth cone controls this amplification process during its navigation through an environment in which basal cue concentrations vary widely. Here, we identified inositol 1,4,5-trisphosphate (IP3) receptor type 3 as a regulator of axonal sensitivity to guidance cues in vitro and in vivo. Growth cones lacking the type 3 subunit are hypersensitive to nerve growth factor (NGF), an IP3-dependent attractive cue, and incapable of turning toward normal concentration ranges of NGF to which wild-type growth cones respond. This is due to globally, but not asymmetrically, activated Ca2+ signaling in the hypersensitive growth cones. Remarkably, lower NGF concentrations can polarize growth cones for turning if IP3 receptor type 3 is deficient. These data suggest a subtype-specific IP3 receptor function in sensitivity adjustment during axon navigation. : Biological Sciences; Neuroscience; Molecular Neuroscience; Cellular Neuroscience Subject Areas: Biological Sciences, Neuroscience, Molecular Neuroscience, Cellular Neuroscience
Keywords	Science ; Q
Subject code	612
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Attenuation of teratoma formation by p27 overexpression in induced pluripotent stem cells.

Matsu-ura, Toru / Sasaki, Hiroshi / Okada, Motoi / Mikoshiba, Katsuhiko / Ashraf, Muhammad

Stem cell research & therapy

2016 Volume 7, Page(s) 30

Abstract: Background: Pluripotent stem cells, such as embryonic stem cells or induced pluripotent stem cells, have a great potential for regenerative medicine. Induced pluripotent stem cells, in particular, are suitable for replacement of tissue by autologous ... ...

Abstract	Background: Pluripotent stem cells, such as embryonic stem cells or induced pluripotent stem cells, have a great potential for regenerative medicine. Induced pluripotent stem cells, in particular, are suitable for replacement of tissue by autologous transplantation. However, tumorigenicity is a major risk in clinical application of both embryonic stem cells and induced pluripotent stem cells. This study explores the possibility of manipulating the cell cycle for inhibition of tumorigenicity. Methods: We genetically modified mouse induced pluripotent stem cells (miPSCs) to overexpress p27 tumor suppressor and examined their proliferation rate, gene expression, cardiac differentiation, tumorigenicity, and therapeutic potential in a mouse model of coronary artery ligation. Results: Overexpression of p27 inhibited cell division of miPSCs, and that inhibition was dependent on the expression level of p27. p27 overexpressing miPSCs had pluripotency characteristics but lost stemness earlier than normal miPSCs during embryoid body and teratoma formation. These cellular characteristics led to none or smaller teratoma when the cells were injected into nude mice. Transplantation of both miPSCs and p27 overexpressing miPSCs into the infarcted mouse heart reduced the infarction size and improved left ventricular function. Conclusions: The overexpression of p27 attenuated tumorigenicity by reducing proliferation and earlier loss of stemness of miPSCs. The overexpression of p27 did not affect pluripotency and differentiation characteristics of miPSC. Therefore, regulation of the proliferation rate of miPSCs offers great therapeutic potential for repair of the injured myocardium.
MeSH term(s)	Animals ; Carcinogenesis/metabolism ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p27/genetics ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Embryoid Bodies/metabolism ; G1 Phase Cell Cycle Checkpoints ; Gene Expression ; Induced Pluripotent Stem Cells/physiology ; Male ; Mice, Inbred C57BL ; Mice, Nude ; Myocardial Infarction/therapy ; Myocardium/pathology ; Stem Cell Transplantation/adverse effects ; Teratoma/etiology ; Teratoma/metabolism ; Teratoma/pathology
Chemical Substances	Cdkn1b protein, mouse ; Cyclin-Dependent Kinase Inhibitor p27 (147604-94-2)
Language	English
Publishing date	2016-02-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-016-0286-3
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Article ; Online: Dual-FRET imaging of IP3 and Ca2+ revealed Ca2+-induced IP3 production maintains long lasting Ca2+ oscillations in fertilized mouse eggs

Toru Matsu-ura / Hideki Shirakawa / Kenichi G. N. Suzuki / Akitoshi Miyamoto / Kotomi Sugiura / Takayuki Michikawa / Akihiro Kusumi / Katsuhiko Mikoshiba

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 11

Abstract: Abstract In most species, fertilization induces Ca2+ transients in the egg. In mammals, the Ca2+ rises are triggered by phospholipase Cζ (PLCζ) released from the sperm; IP3 generated by PLCζ induces Ca2+ release from the intracellular Ca2+ store through ... ...

Abstract	Abstract In most species, fertilization induces Ca2+ transients in the egg. In mammals, the Ca2+ rises are triggered by phospholipase Cζ (PLCζ) released from the sperm; IP3 generated by PLCζ induces Ca2+ release from the intracellular Ca2+ store through IP3 receptor, termed IP3-induced Ca2+ release. Here, we developed new fluorescent IP3 sensors (IRIS-2s) with the wider dynamic range and higher sensitivity (Kd = 0.047–1.7 μM) than that we developed previously. IRIS-2s employed green fluorescent protein and Halo-protein conjugated with the tetramethylrhodamine ligand as fluorescence resonance energy transfer (FRET) donor and acceptor, respectively. For simultaneous imaging of Ca2+ and IP3, using IRIS-2s as the IP3 sensor, we developed a new single fluorophore Ca2+ sensor protein, DYC3.60. With IRIS-2s and DYC3.60, we found that, right after fertilization, IP3 concentration ([IP3]) starts to increase before the onset of the first Ca2+ wave. [IP3] stayed at the elevated level with small peaks followed after Ca2+ spikes through Ca2+ oscillations. We detected delays in the peak of [IP3] compared to the peak of each Ca2+ spike, suggesting that Ca2+-induced regenerative IP3 production through PLC produces small [IP3] rises to maintain [IP3] over the basal level, which results in long lasting Ca2+ oscillations in fertilized eggs.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition.

Liu, Xiao / Dang, Yunkun / Matsu-Ura, Toru / He, Yubo / He, Qun / Hong, Christian I / Liu, Yi

Molecular cell

2017 Volume 67, Issue 2, Page(s) 203–213.e4

Abstract: Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here, we show that DNA replication is ... ...

Abstract	Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here, we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter. The FACT complex, known to be involved in histone disassembly/reassembly, is required for clock function and is recruited to the frq promoter in a replication-dependent manner to promote replacement of histone H2A.Z by H2A. Finally, deletion of H2A.Z uncoupled the dependence of the circadian clock on DNA replication. Together, these results establish circadian clock and cell cycle as interdependent coupled oscillators and identify DNA replication as a critical process in the circadian mechanism.
MeSH term(s)	Animals ; Circadian Clocks ; Circadian Rhythm ; DNA Replication ; DNA, Fungal/chemistry ; DNA, Fungal/genetics ; DNA, Fungal/metabolism ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Gene Expression Regulation, Fungal ; High Mobility Group Proteins/genetics ; High Mobility Group Proteins/metabolism ; Histones/genetics ; Histones/metabolism ; Neurospora/genetics ; Neurospora/metabolism ; Nucleic Acid Conformation ; Nucleosomes/chemistry ; Nucleosomes/genetics ; Nucleosomes/metabolism ; Proliferating Cell Nuclear Antigen/genetics ; Proliferating Cell Nuclear Antigen/metabolism ; Promoter Regions, Genetic ; Protein Conformation ; Structure-Activity Relationship ; Time Factors ; Transcription, Genetic ; Transcriptional Elongation Factors/genetics ; Transcriptional Elongation Factors/metabolism
Chemical Substances	DNA, Fungal ; FRQ protein, Neurospora crassa ; Fungal Proteins ; High Mobility Group Proteins ; Histones ; Nucleosomes ; Proliferating Cell Nuclear Antigen ; Transcriptional Elongation Factors
Language	English
Publishing date	2017-06-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2017.05.029
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Zs.A 5055: Show issues

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Article ; Online: Phospholipase C-β1 and β4 contribute to non-genetic cell-to-cell variability in histamine-induced calcium signals in HeLa cells.

Ishida, Sachiko / Matsu-Ura, Toru / Fukami, Kiyoko / Michikawa, Takayuki / Mikoshiba, Katsuhiko

PloS one

2014 Volume 9, Issue 1, Page(s) e86410

Abstract: A uniform extracellular stimulus triggers cell-specific patterns of Ca(2+) signals, even in genetically identical cell populations. However, the underlying mechanism that generates the cell-to-cell variability remains unknown. We monitored cytosolic ... ...

Abstract	A uniform extracellular stimulus triggers cell-specific patterns of Ca(2+) signals, even in genetically identical cell populations. However, the underlying mechanism that generates the cell-to-cell variability remains unknown. We monitored cytosolic inositol 1,4,5-trisphosphate (IP3) concentration changes using a fluorescent IP3 sensor in single HeLa cells showing different patterns of histamine-induced Ca(2+) oscillations in terms of the time constant of Ca(2+) spike amplitude decay and the Ca(2+) oscillation frequency. HeLa cells stimulated with histamine exhibited a considerable variation in the temporal pattern of Ca(2+) signals and we found that there were cell-specific IP3 dynamics depending on the patterns of Ca(2+) signals. RT-PCR and western blot analyses showed that phospholipase C (PLC)-β1, -β3, -β4, -γ1, -δ3 and -ε were expressed at relatively high levels in HeLa cells. Small interfering RNA-mediated silencing of PLC isozymes revealed that PLC-β1 and PLC-β4 were specifically involved in the histamine-induced IP3 increases in HeLa cells. Modulation of IP3 dynamics by knockdown or overexpression of the isozymes PLC-β1 and PLC-β4 resulted in specific changes in the characteristics of Ca(2+) oscillations, such as the time constant of the temporal changes in the Ca(2+) spike amplitude and the Ca(2+) oscillation frequency, within the range of the cell-to-cell variability found in wild-type cell populations. These findings indicate that the heterogeneity in the process of IP3 production, rather than IP3-induced Ca(2+) release, can cause cell-to-cell variability in the patterns of Ca(2+) signals and that PLC-β1 and PLC-β4 contribute to generate cell-specific Ca(2+) signals evoked by G protein-coupled receptor stimulation.
MeSH term(s)	Blotting, Western ; Calcium Signaling/drug effects ; Calcium Signaling/physiology ; Cytosol/metabolism ; DNA Primers/genetics ; HeLa Cells ; Histamine/metabolism ; Histamine/pharmacology ; Humans ; Inositol 1,4,5-Trisphosphate/metabolism ; Isoenzymes/metabolism ; Phospholipase C beta/metabolism ; RNA Interference ; RNA, Small Interfering/genetics ; Receptors, G-Protein-Coupled/metabolism ; Reverse Transcriptase Polymerase Chain Reaction
Chemical Substances	DNA Primers ; Isoenzymes ; RNA, Small Interfering ; Receptors, G-Protein-Coupled ; Histamine (820484N8I3) ; Inositol 1,4,5-Trisphosphate (85166-31-0) ; Phospholipase C beta (EC 3.1.4.11)
Language	English
Publishing date	2014-01-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0086410
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