A5077161039- Pluripotent Stem Cells Research
- Cellular Mechanics and Interactions
- Retinal Development and Disorders
- Neuroscience and Neural Engineering
- 3D Printing in Biomedical Research
- Neurogenesis and neuroplasticity mechanisms
- Photoreceptor and optogenetics research
- Developmental Biology and Gene Regulation
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Tissue Engineering and Regenerative Medicine
- Congenital heart defects research
- Mathematical Biology Tumor Growth
- Neuroscience and Neuropharmacology Research
- Planarian Biology and Electrostimulation
- Genetics, Aging, and Longevity in Model Organisms
- Infant Health and Development
- Biomedical Ethics and Regulation
- Gastrointestinal motility and disorders
- Photochromic and Fluorescence Chemistry
- Olfactory and Sensory Function Studies
- Neurobiology and Insect Physiology Research
- Biochemical Analysis and Sensing Techniques
- Nerve injury and regeneration
- Renal and related cancers
Kyoto University
2005-2025
RIKEN Center for Biosystems Dynamics Research
2015-2022
RIKEN Center for Computational Science
2012-2017
RIKEN
2012-2017
Genesis Research Institute
2008-2014
RIKEN Center for Brain Science
2005-2011
Organogenesis (United States)
2008
Japan Science and Technology Agency
2002-2005
Significance Using 3D culture of human ES cells, we show new self-organizing aspects corticogenesis: spontaneous development intracortical polarity, curving morphology, and complex zone separations. Moreover, this generates species-specific progenitors, outer radial glia, which are abundantly present in the human, but not mouse, neocortex. Our study suggests an unexpectedly wide range events that driven by internal programs neocortex development.
Abstract The developing dorsomedial telencephalon includes the medial pallium, which goes on to form hippocampus. Generating a reliable source of human hippocampal tissue is an important step for cell-based research into hippocampus-related diseases. Here we show generation functional granule- and pyramidal-like neurons from self-organizing telencephalic using embryonic stem cells (hESCs). First, develop hESC culture method that utilizes bone morphogenetic protein (BMP) Wnt signalling induce...
In this article, we show that mouse embryonic stem cell- or induced pluripotent cell-derived 3D retinal tissue developed a structured outer nuclear layer (ONL) with complete inner and segments even in an advanced degeneration model (rd1) lacked ONL. We also observed host-graft synaptic connections by immunohistochemistry. This study provides "proof of concept" for sheet transplantation therapy degenerative diseases.
In the developing neural retina (NR), multipotent stem cells within ciliary margin (CM) contribute to de novo retinal tissue growth. We recently reported ability of human embryonic (hESCs) self-organize stratified NR using a three-dimensional culture technique. Here we report emergence CM-like cell niches tissue. First, developed method for selective differentiation by timed BMP4 treatment. then found that inhibiting GSK3 and FGFR induced transition from pigment epithelium (RPE), removing...
Significance We first confirmed the ability of human embryonic stem cell-derived retina (hESC-retina) to form structured mature photoreceptor layers after transplantation into nude rats. then developed two monkey models retinal degeneration and evaluated their utility as host for studies. Finally, we performed a pilot study hESC-retina in conducted vivo monitoring studies using clinical devices subsequently graft maturation potential formation synaptic contacts between cells. This...
Abstract Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable homeostasis. For this reason, generating human anterior tissue that retains regulatory control in vitro an important step the development of cell transplantation therapy diseases. Here we achieve by recapitulating mouse using embryonic stem cells. We find self-forms following co-induction hypothalamic oral ectoderm. The juxtaposition these tissues...
Embryonic stem (ES) cells differentiate into neuroectodermal progenitors when cultured as floating aggregates in serum-free conditions. Here, we show that strict removal of exogenous patterning factors during early differentiation steps induces efficient generation rostral hypothalamic-like (Rax(+)/Six3(+)/Vax1(+)) mouse ES cell-derived cells. The use growth factor-free chemically defined medium is critical and even the presence insulin, which commonly used cell culture, strongly inhibits...
During early telencephalic development, the major portion of ventral (subpallial) region becomes subdivided into three regions, lateral (LGE), medial (MGE), and caudal (CGE) ganglionic eminences. In this study, we systematically recapitulated subpallial patterning in mouse embryonic stem cell (ESC) cultures investigated temporal combinatory actions signals. serum-free floating culture, dorsal-ventral specification ESC-derived neuroectoderm is dose-dependently directed by Sonic hedgehog (Shh)...
We have previously reported that xeno-transplanted human ESC-derived retinas are able to mature in the immunodeficient retinal degeneration rodent models, similar allo-transplantations using mouse iPSC-derived retina. The photoreceptors latter developed outer segments and formed synapses with host bipolar cells, driving light responses of ganglion cells. In view clinical application, here we further confirmed competency retina (hiPSC-retina) degenerated rat monkey models.Human iPSC-retinas...
Highlights•Two mouse models of immunodeficient end-stage retinal degeneration were established•Immunodeficient host permitted transplantation human ESC-derived sheets•Transplanted sheets survived long term and maturated•After transplantation, light responses recorded from the degenerated retinaSummaryIncreasing demand for clinical therapies featuring ESC/iPSC-derived tissue cells warrants proof-of-concept studies. Here, we established two with immunodeficiency, NOG-rd1-2J NOG-rd10,...
Organogenesis is a self-organizing process of multiple cells in three-dimensional (3D) space, where macroscopic tissue deformations are robustly regulated by multicellular autonomy. It clear that this robust regulation requires to sense and modulate 3D formation across different scales, but its underlying mechanisms still unclear. To address question, we developed versatile computational model dynamics at single-cell resolution combined it with the culture system pluripotent stem...
The emerging field of synthetic developmental biology proposes bottom-up approaches to examine the contribution each cellular process complex morphogenesis. However, shortage tools manipulate three-dimensional (3D) shapes mammalian tissues hinders progress field. Here we report development OptoShroom3, an optogenetic tool that achieves fast spatiotemporal control apical constriction in epithelia. Activation OptoShroom3 through illumination epithelial Madin-Darby Canine Kidney (MDCK) cell...
In the mammalian cortex, dorsal telencephalon exhibits a characteristic stratified structure. We previously reported that three-dimensional (3D) culture of mouse ES cells (mESCs) can efficiently generate cortical neuroepithelium (NE) and layer-specific neurons. However, NE generated in this mESC was structurally unstable broke into small neural rosettes by day 7, suggesting some factors for reinforcing structural integrity were missing. Here we report substantial supporting effects...
Abstract This study demonstrates computational simulations of multicellular deformation coupled with chemical patterning in the three-dimensional (3D) space. To address these aspects, we proposes a novel mathematical model, where reaction–diffusion system is discretely expressed at single cell level and combined 3D vertex model. investigate complex phenomena emerging from coupling deformation, as an example, employed activator–inhibitor converted activator concentration individual cells into...
We have identified a novel epidermal growth factor (EGF)-like repeat-containing single-pass transmembrane protein that is specifically expressed in the developing and mature central nervous system. Sequence analysis revealed 10 EGF-like repeats extracellular domain are closely related to those of developmentally important receptor Notch its ligand Delta. thus named molecule Delta/Notch-like EGF-related (DNER). DNER strongly several types post-mitotic neurons, including cortical hippocampal...
Abstract The generation of complex organ structures such as the eye requires intricate orchestration multiple cellular interactions. In this paper, early retinal development is discussed with respect to structure formation optic cup. Although recent studies have elucidated molecular mechanisms differentiation, little known about how unique shape cup determined. A report has demonstrated that optic‐cup morphogenesis spontaneously occurs in three‐dimensional stem‐cell culture without external...