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This study analyzes gene expression across single cells of the human neocortex. The authors find that outer radial glia preferentially express genes related to extracellular matrix formation, migration, and stemness, including TNC, PTPRZ1, FAM107A, HOPX, and LIFR. Using dynamic imaging, immunostaining, and clonal analysis, they relate these molecular features to distinctive behaviors of outer radial glia and demonstrate the necessity of STAT3 signaling for their cell cycle progression.
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This study analyzes the transcriptomes of distinct progenitor subpopulations isolated by a cell polarity-based approach from developing mouse and human neocortex. They identify genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs, specifically ARHGAP11B, which has a high degree of radial glia-specific expression. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal and can increase cortical plate area and induce gyrification. The authors conclude that ARHGAP11B may have contributed to evolutionary expansion of human neocortex.
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Cerebral organoids model human brain development and microcephaly
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This study describes a human pluripotent stem cell-derived three-dimensional organoid culture system that develops structures that resemble various brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. The study uses RNA interference and patient-specific induced pluripotent stem cells to model microcephaly. They demonstrate that patient organoids undergo premature neuronal differentiation, a defect that could help to explain the disease phenotype.
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39• Lancaster, M.A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L.S., Hurles, M.E., Homfray, T., Penninger, J.M., Jackson, A.P., Knoblich, J.A., Cerebral organoids model human brain development and microcephaly. Nature 501 (2013), 373–379 This study describes a human pluripotent stem cell-derived three-dimensional organoid culture system that develops structures that resemble various brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. The study uses RNA interference and patient-specific induced pluripotent stem cells to model microcephaly. They demonstrate that patient organoids undergo premature neuronal differentiation, a defect that could help to explain the disease phenotype.
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Lancaster, M.A.1
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Wenzel, D.4
Bicknell, L.S.5
Hurles, M.E.6
Homfray, T.7
Penninger, J.M.8
Jackson, A.P.9
Knoblich, J.A.10
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40
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84877301288
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Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development
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40 Nicholas, C.R., Chen, J., Tang, Y., Southwell, D.G., Chalmers, N., Vogt, D., Arnold, C.M., Chen, Y.-J.J., Stanley, E.G., Elefanty, A.G., et al. Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development. Cell Stem Cell 12 (2013), 573–586.
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Cell Stem Cell
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Nicholas, C.R.1
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Chalmers, N.5
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Arnold, C.M.7
Chen, Y.-J.J.8
Stanley, E.G.9
Elefanty, A.G.10
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41
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84934442315
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Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture
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41 Paşca, A.M., Sloan, S.A., Clarke, L.E., Tian, Y., Makinson, C.D., Huber, N., Kim, C.H., Park, J.-Y., O'Rourke, N.A., Nguyen, K.D., et al. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Chem Biol 12 (2015), 671–678.
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Paşca, A.M.1
Sloan, S.A.2
Clarke, L.E.3
Tian, Y.4
Makinson, C.D.5
Huber, N.6
Kim, C.H.7
Park, J.-Y.8
O'Rourke, N.A.9
Nguyen, K.D.10
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42
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84962090418
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2D and 3D stem cell models of primate cortical development identify species-specific differences in progenitor behavior contributing to brain size
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42 Otani, T., Marchetto, M.C., Gage, F.H., Simons, B.D., Livesey, F.J., 2D and 3D stem cell models of primate cortical development identify species-specific differences in progenitor behavior contributing to brain size. Cell Stem Cell 18 (2016), 467–480.
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Otani, T.1
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43
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iPSCs: a minireview from bench to bed, including organoids and the CRISPR system
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43 Orqueda, A.J., Giménez, C.A., Pereyra-Bonnet, F., iPSCs: a minireview from bench to bed, including organoids and the CRISPR system. Stem Cells Int, 2016, 2016, 5934782.
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Orqueda, A.J.1
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44
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Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses
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44 Shi, Y., Shi, Y., Kirwan, P., Kirwan, P., Smith, J., Smith, J., Robinson, H.P.C., Robinson, H.P.C., Livesey, F.J., Livesey, F.J., Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. Nat Neurosci 15 (2012), 477–486 S1.
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Shi, Y.1
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Robinson, H.P.C.7
Robinson, H.P.C.8
Livesey, F.J.9
Livesey, F.J.10
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45
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84890282623
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Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex
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45 Kadoshima, T., Sakaguchi, H., Nakano, T., Soen, M., Ando, S., Eiraku, M., Sasai, Y., Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex. Proc Natl Acad Sci U S A 110 (2013), 20284–20289.
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Kadoshima, T.1
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Ando, S.5
Eiraku, M.6
Sasai, Y.7
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46
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84964619895
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Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure
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This study develops a revised protocol for cerebral organoid generation, which they employ to model Zika virus (ZIKV) exposure. Quantitative analyses reveals preferential, productive infection of neural progenitors with either African or Asian ZIKV strains. ZIKV infection leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell-layer volume resembling microcephaly.
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46•• Qian, X., Nguyen, H.N., Song, M.M., Hadiono, C., Ogden, S.C., Hammack, C., Yao, B., Hamersky, G.R., Jacob, F., Zhong, C., et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165 (2016), 1238–1254 This study develops a revised protocol for cerebral organoid generation, which they employ to model Zika virus (ZIKV) exposure. Quantitative analyses reveals preferential, productive infection of neural progenitors with either African or Asian ZIKV strains. ZIKV infection leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell-layer volume resembling microcephaly.
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(2016)
Cell
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Qian, X.1
Nguyen, H.N.2
Song, M.M.3
Hadiono, C.4
Ogden, S.C.5
Hammack, C.6
Yao, B.7
Hamersky, G.R.8
Jacob, F.9
Zhong, C.10
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