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Publication

Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells.

Cell | 2016

Understanding human embryonic ventral midbrain is of major interest for Parkinson's disease. However, the cell types, their gene expression dynamics, and their relationship to commonly used rodent models remain to be defined. We performed single-cell RNA sequencing to examine ventral midbrain development in human and mouse. We found 25 molecularly defined human cell types, including five subtypes of radial glia-like cells and four progenitors. In the mouse, two mature fetal dopaminergic neuron subtypes diversified into five adult classes during postnatal development. Cell types and gene expression were generally conserved across species, but with clear differences in cell proliferation, developmental timing, and dopaminergic neuron development. Additionally, we developed a method to quantitatively assess the fidelity of dopaminergic neurons derived from human pluripotent stem cells, at a single-cell level. Thus, our study provides insight into the molecular programs controlling human midbrain development and provides a foundation for the development of cell replacement therapies.

Pubmed ID: 27716510 RIS Download

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Associated grants

Agency: European Research Council, International
Id: 261063
Agency: Medical Research Council, United Kingdom
Id: MC_PC_12009

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This is a list of tools and resources that we have found mentioned in this publication.

Allen Mouse Brain Reference Atlas (tool)

RRID:SCR_002978

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Allen Developing Mouse Brain Atlas (tool)

RRID:SCR_002990

Map of gene expression in developing mouse brain revealing gene expression patterns from embryonic through postnatal stages. Provides information about spatial and temporal regulation of gene expression with database. Feature include seven sagittal reference atlases created with a developmental ontology. These anatomic atlases may be viewed alongside in situ hybridization (ISH) data as well as by itself.

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scikit-learn (tool)

RRID:SCR_002577

scikit-learn: machine learning in Python

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Novus Biologicals (tool)

RRID:SCR_004286

Commercial antibody vendor which supplies antibodies and other products to life science researchers.

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Human Frontier Science Program (tool)

RRID:SCR_005112

The HFSP supports novel, innovative and interdisciplinary basic research focused on the complex mechanisms of living organisms; topics range from molecular and cellular approaches to systems and cognitive neuroscience. A clear emphasis is placed on novel collaborations that bring biologists together with scientists from fields such as physics, mathematics, chemistry, computer science and engineering to focus on problems at the frontier of the life sciences. The Trust provides funding for research regarding complex biological systems. It offers research grants, post doc fellowships, career development fellowships, and short- long- and cross- disciplinary fellowships. HFSP funding programs are strictly project-related and begin at the postdoctoral level. We have no support for PhD students nor for travel grants to scientific meetings. Nor do we provide sponsorship or funds to organizers of scientific meetings. Research Grants Research Grants are awarded for novel collaborations involving extensive collaboration among teams of scientists working in different countries and in different disciplines. Two types of grants are available: Young Investigators Grants and Program Grants. Postdoctoral Fellowships Postdoctoral Fellowships are available for scientists who wish to work in foreign laboratories, with emphasis on individuals early in their careers who wish to obtain training in a different field of research. Fellows who return to their home countries or move to an HFSP member country that is different from the Fellowship host country are eligible to apply for a Career Development Award. Long-Term Fellowships are for scientists with a Ph.D. degree in the life sciences who wish to broaden their experience through postdoctoral training abroad. Cross-Disciplinary Fellowships are intended for postdoctoral fellows with a Ph.D. degree in the physical sciences, chemistry, mathematics, engineering and computer sciences who wish to receive training in biology. Career Development Awards Career Development Awards are for former HFSP Long-Term or Cross-Disciplinary Fellows who return to their home country or move to an HFSP member country that is different from the host country of their HFSP Fellowship. The award provides support for initiating the fellows'' first independent laboratory.

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QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

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NumPy (tool)

RRID:SCR_008633

NumPy is the fundamental package needed for scientific computing with Python. It contains among other things: * a powerful N-dimensional array object * sophisticated (broadcasting) functions * tools for integrating C/C and Fortran code * useful linear algebra, Fourier transform, and random number capabilities. Besides its obvious scientific uses, NumPy can also be used as an efficient multi-dimensional container of generic data. Arbitrary data-types can be defined. This allows NumPy to seamlessly and speedily integrate with a wide variety of databases. Sponsored by ENTHOUGHT

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PeerJ Article Repository (tool)

RRID:SCR_014698

An article repository which archives peer-reviewed papers and non-peer-reviewed preprints in PeerJ. It includes papers and preprints from the biological and medical sciences PeerJ journal and from the computer science PeerJ journal.

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GitHub (tool)

RRID:SCR_002630

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SciPy (tool)

RRID:SCR_008058

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Adobe Illustrator (tool)

RRID:SCR_010279

Vector graphics software to create digital graphics, illustrations, and typography for several types of media: print, web, interactive, video, and mobile.

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PANTHER (tool)

RRID:SCR_015893

System that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.

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