Title | Specification of positional identity in forebrain organoids. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Cederquist GY, Asciolla JJ, Tchieu J, Walsh RM, Cornacchia D, Resh MD, Studer L |
Journal | Nat Biotechnol |
Volume | 37 |
Issue | 4 |
Pagination | 436-444 |
Date Published | 2019 04 |
ISSN | 1546-1696 |
Keywords | Animals, Biotechnology, Body Patterning, Cell Differentiation, Cholesterol, Hedgehog Proteins, Humans, Mice, Models, Neurological, Neural Stem Cells, Neurogenesis, Organoids, Pluripotent Stem Cells, Prosencephalon, Signal Transduction |
Abstract | Human brain organoids generated with current technologies recapitulate histological features of the human brain, but they lack a reproducible topographic organization. During development, spatial topography is determined by gradients of signaling molecules released from discrete signaling centers. We hypothesized that introduction of a signaling center into forebrain organoids would specify the positional identity of neural tissue in a distance-dependent manner. Here, we present a system to trigger a Sonic Hedgehog (SHH) protein gradient in developing forebrain organoids that enables ordered self-organization along dorso-ventral and antero-posterior positional axes. SHH-patterned forebrain organoids establish major forebrain subdivisions that are positioned with in vivo-like topography. Consistent with its behavior in vivo, SHH exhibits long-range signaling activity in organoids. Finally, we use SHH-patterned cerebral organoids as a tool to study the role of cholesterol metabolism in SHH signaling. Together, this work identifies inductive signaling as an effective organizing strategy to recapitulate in vivo-like topography in human brain organoids. |
DOI | 10.1038/s41587-019-0085-3 |
Alternate Journal | Nat. Biotechnol. |
PubMed ID | 30936566 |
PubMed Central ID | PMC6447454 |
Grant List | F30 MH113343 / MH / NIMH NIH HHS / United States R01 AG054720 / AG / NIA NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States T32 GM008539 / GM / NIGMS NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
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