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Functioning brain tissue grown in 3-D structure
CALB and L7 are Purkinje-cell specific late markers are shown. GRID2 is a marker for a Purkinje-specific glutamate receptor. LHX5 is a marker for early Purkinje cells. Credit: RIKEN
Researchers at the RIKEN Center for Developmental Biology in Japan have succeeded in inducing human embryonic stem cells to self-organize into a three-dimensional structure similar to the cerebellum, providing tantalizing clues in the quest to recreate neural structures in the laboratory. One of the primary goals of stem-cell research is to be able to replace damaged body parts with tissues grown from undifferentiated stem cells. For the nervous system, this is a particular challenge because not only do specific neurons need to be generated, but they must also be coaxed into connecting to each other in very specific ways.
RIKEN researchers have taken up this challenge, and the work published in Cell Reports details how sequentially applying several signaling molecules to three-dimensional cultures of human embryotic stem cells prompts the cells to differentiate into functioning cerebellar neurons that self-organize to form the proper dorsal/ventral patterning and multi-layer structure found in the natural developing cerebellum.
Expanding from their previous studies with mice, the researchers first established that under specific conditions, culturing human embryonic stem cells with fibroblast growth factor 2 (FGF2) leads to neural differentiation particular to the midbrain/hindbrain region -- the location of the cerebellum -- within three weeks, and the expression of markers for the cerebellar plate neuroepithelium -- the part of the developing nervous system specific for the cerebellum -- within five. These cells also showed early markers that are specific to developing Purkinje cells, granule cells, or deep cerebellar projection neurons -- all types of neurons only found in the cerebellum.
The researchers then looked for mature cerebellar neurons. They found that cells treated with FGF2 expressed late Purkinje-cell markers and developed structures characteristic of those cells. Electrophysiological recordings of these cells after culture for about 15 weeks revealed proper responses to currents and to inhibition of receptors needed for normal cerebellar signaling, indicating that function had developed along with structure. Some FGF2-treated cells also expressed markers for the rhombic lip -- the structure from which granule cells develop and migrate, and a marker specific to migrating granule precursors by week seven. Moreover, cells were seen to migrate and extend fibers that bent to form the T-shape characteristic of granule cell parallel fibers.
Where these neurons form and how they locate in relation to each other is critical in the developing brain. Early in cerebellar development, particular cell types come to be distributed unevenly from top to bottom, creating a dorsal-ventral separation. Researchers tested several factors, and found that adding FGF19 around day 14 to the FGF2-treated cells caused several flat oval neuroepithelium to form by day 35, expressing dorsal-specific markers on the outside and ventral-specific markers on the inside. By adding stromal cell-derived factor 1 (SDF1) between days 28-35, they were able to generate a continuous neuroepithelial structure with dorsal-ventral polarity.
SDF1 also induced two other important structural changes. The dorsal region spontaneously developed three layers along the dorsal-ventral axis: the ventricular zone, a Purkinje-cell precursor zone, and a rhombic lip zone. At one end of the neuroepithelium, a region developed that was positive for markers of progenitors of granule and deep cerebellar nuclei projection neurons and negative for Purkinje-cell markers, and whose origins could be traced to the rhombic lip zone of the cerebellar plate.
Lead author Keiko Muguruma says that, "the principles of self-organization that we have demonstrated here are important for the future of developmental biology." She added that, "attempts to generate the cerebellum from human iPS cells have already met with some success, and these patient-derived cerebellar neurons and tissues will be useful for modeling cerebellar diseases such as spinocerebellar ataxia."
Story Source:
The above story is based on materials provided by RIKEN. Note: Materials may be edited for content and length.
Journal Reference:
- Keiko Muguruma, Ayaka Nishiyama, Hideshi Kawakami, Kouichi Hashimoto, Yoshiki Sasai. Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. Cell Reports, 2015 DOI: 10.1016/j.celrep.2014.12.051
Source: http://www.sciencedaily.com/releases/2015/01/150129125430.htm
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Founded by Russian entrepreneur Dmitry Itskov in February 2011 with the participation of leading Russian specialists in the field of neural interfaces, robotics, artificial organs and systems.
The main goals of the 2045 Initiative: the creation and realization of a new strategy for the development of humanity which meets global civilization challenges; the creation of optimale conditions promoting the spiritual enlightenment of humanity; and the realization of a new futuristic reality based on 5 principles: high spirituality, high culture, high ethics, high science and high technologies.
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A large-scale transformation of humanity, comparable to some of the major spiritual and sci-tech revolutions in history, will require a new strategy. We believe this to be necessary to overcome existing crises, which threaten our planetary habitat and the continued existence of humanity as a species. With the 2045 Initiative, we hope to realize a new strategy for humanity's development, and in so doing, create a more productive, fulfilling, and satisfying future.
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Future prospects of "2045" Initiative for society
2015-2020
The emergence and widespread use of affordable android "avatars" controlled by a "brain-computer" interface. Coupled with related technologies “avatars’ will give people a number of new features: ability to work in dangerous environments, perform rescue operations, travel in extreme situations etc.
Avatar components will be used in medicine for the rehabilitation of fully or partially disabled patients giving them prosthetic limbs or recover lost senses.
2020-2025
Creation of an autonomous life-support system for the human brain linked to a robot, ‘avatar’, will save people whose body is completely worn out or irreversibly damaged. Any patient with an intact brain will be able to return to a fully functioning bodily life. Such technologies will greatly enlarge the possibility of hybrid bio-electronic devices, thus creating a new IT revolution and will make all kinds of superimpositions of electronic and biological systems possible.
2030-2035
Creation of a computer model of the brain and human consciousness with the subsequent development of means to transfer individual consciousness onto an artificial carrier. This development will profoundly change the world, it will not only give everyone the possibility of cybernetic immortality but will also create a friendly artificial intelligence, expand human capabilities and provide opportunities for ordinary people to restore or modify their own brain multiple times. The final result at this stage can be a real revolution in the understanding of human nature that will completely change the human and technical prospects for humanity.
2045
This is the time when substance-independent minds will receive new bodies with capacities far exceeding those of ordinary humans. A new era for humanity will arrive! Changes will occur in all spheres of human activity – energy generation, transportation, politics, medicine, psychology, sciences, and so on.
Today it is hard to imagine a future when bodies consisting of nanorobots will become affordable and capable of taking any form. It is also hard to imagine body holograms featuring controlled matter. One thing is clear however: humanity, for the first time in its history, will make a fully managed evolutionary transition and eventually become a new species. Moreover, prerequisites for a large-scale expansion into outer space will be created as well.
Key elements of the project in the future
• International social movement
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• annual award for contribution to the realization of the project of "Immortality”.
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