Cerebral Organoids Model Human Brain Development and Microcephaly
2013 · paper · Biomedicine
Develops a 3D culture from human pluripotent stem cells that forms discrete brain regions and recapitulates features of human cortical development. Using patient-derived cells, it models microcephaly and shows premature neuronal differentiation in patient organoids.
Checked: PDF from europepmc.org, fetched 4 Oct 2026. Page numbers are those of that PDF.
1 finding
Reference or label "which are only present to a limited degree in rodents5" cites Smart et al. 2002 (monkey cortex), while "completely absent in mice6" cites Shitamukai et al. 2011 (mouse oRG-like progenitors); the two citations appear transposed.
- p. 1 Introduction, para 1
which are only present to a limited degree in rodents5
- p. 2 Introduction, top line
completely absent in mice6
- p. 12 Reference 5
extrastriate cortex in the monkey. Cereb. Cortex. 2002; 12:37–53.
- p. 12 Reference 6
Oblique radial glial divisions in the developing mouse neocortex induce self-renewing progenitors outside the germinal zone
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: what Smart et al. 2002 and Shitamukai et al. 2011 actually report, beyond their titles. From the titles on p12, ref 5 concerns 'striate and extrastriate cortex in the monkey' and ref 6 concerns mouse neocortex progenitors 'that resemble primate outer subventricular zone progenitors'. Ref 6 matches the rodent oRG claim and ref 5 matches the primate IFL/OSVZ claim, which suggests a swap. Only the authors can confirm the intended citations.
Second check: another model agreed
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18 minor (typos and the like; most checked by the judge only)
Wording "We observed mainly horizontal orientations (41%)" describes a plurality as 'mainly'; Fig. 3h shows 41% horizontal vs 37% oblique and 22% vertical (n=27).
- p. 5 Results, spindle orientation paragraph
We observed mainly horizontal orientations (41%)
- p. 17 Figure 3h bar chart
41%
Judge's note: Fig. 3h on p17 shows bars of 41%, 37% and 22%, with n=27. The 41% is printed right next to the claim and the text immediately notes 'abundant oblique (37%) and vertical (22%)', so this is only loose wording.
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Wording "the vast majority of oRGs divided vertically (Figure 5d)" while Fig. 5d shows 64% vertical (60-90°), 29% oblique and 7% horizontal (n=14).
- p. 6 Results, oRG paragraph
the vast majority of oRGs divided vertically (Figure 5d)
- p. 19 Figure 5d bar chart
64%
- p. 19 Figure 5d bar chart and legend
Quantification of spindle orientation for 14 anaphase oRGs from 6 different cortical tissues.
Judge's note: The Fig. 5d bar chart on p19 shows 7%, 29% and 64%, with n=14. That is consistent with 1, 4 and 9 cells. Vertical divisions are a majority, but 'vast majority' overstates 64%.
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Typo Author Contributions abbreviates Matthew E. Hurles as "M.H." although other authors with middle initials get them (M.A.L., L.S.B., J.M.P., A.P.J.), and "M.A.L and J.A.K." lacks the final period.
- p. 1 Author Contributions footnote
L.S.B., M.H., and T.H. performed patient diagnosis
- p. 1 Author list
Matthew E. Hurles
Judge's note: The author list on p1 shows 'Matthew E. Hurles'. The footnote reads 'L.S.B., M.H., and T.H. performed patient diagnosis' and opens with 'M.A.L and J.A.K.' with no period after L. Both are cosmetic inconsistencies and the identity is unambiguous.
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Typo Doubled full stop in the correspondence line: "(juergen.knoblich@imba.oeaw.ac.at).."
- p. 1 Correspondence line
juergen.knoblich@imba.oeaw.ac.at)..
Judge's note: The page image on p1 shows two periods after the closing parenthesis.
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Typo Supplementary Text: "Development milestones were mildly/moderately delayed"; the usual term is 'Developmental milestones'
- p. 12 Patient clinical synopsis
Development milestones were mildly/
- p. 1 Supplementary Text
Development milestones were mildly/moderately delayed
Judge's note: The p12 image shows 'Development milestones'. The meaning is clear, so this is only a wording/cosmetic point.
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Typo Wrong verb form after a modal: "neurons within cerebral organoids could exhibited neural activity" (should be "could exhibit").
- p. 5 Results, Formation of functional cerebral cortical neurons, last paragraph
could exhibited neural activity
- p. 5 Results, last paragraph
neurons within cerebral organoids could exhibited neural activity
- p. 9 Live imaging
Change is fluorescence
- p. 9 Live imaging
Fbasal))/Fbackground
Judge's note: Seen in the page image (p5, last paragraph). Reviewer note 4 also raises the 'Change is fluorescence' and parenthesis issues on p9; those are adjudicated under C010.
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Typo First author capitalised "LaMonica et al." in the text (p6) but "Lamonica BE" in reference 36 (p14).
- p. 6 Results, oRG paragraph
described by LaMonica et al.
- p. 14 Reference 36
Lamonica BE, Lui JH, Hansen DV, Kriegstein AR.
- p. 6 Results, oRG paragraph
described by LaMonica et al. in human brain
- p. 6 Recapitulation of human cerebral cortical organization
LaMonica et al.
Judge's note: Both forms appear in the page images. Within the files this is a cosmetic inconsistency. That 'LaMonica' is the correct form rests on outside knowledge.
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Typo Methods (p11) say "peripheral blood of Patient 3842", while the Supplementary Text and Figure 6 legend call the patient "A3842"
- p. 11 Methods, Research subject and gene identification
peripheral blood of Patient 3842
- p. 11 Supplementary Text, Patient clinical synopsis
Patient A3842 exhibited growth restriction
- p. 11 Research subject
Patient 3842
- p. 6 Microcephaly section
Supplemental Text
Judge's note: C016-a shows 'Patient 3842' in Methods. C016-b and the Figure 6 legend (p20) show 'A3842'. It is clearly the same patient, so this is a cosmetic inconsistency in the identifier. The 'Supplemental Text' versus 'Supplementary Text' point is not a defect: the paper and supplement use both forms (e.g. 'Supplemental Video'), and the pointer resolves without doubt.
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Typo "Change is fluorescence was calculated as follows: ΔF/F=(F-Fbasal))/Fbackground" has 'is' for 'in' and an unmatched extra closing parenthesis.
- p. 9 Methods, Live imaging in organoids
Change is fluorescence was calculated as follows
- p. 9 Live imaging in organoids
Change is fluorescence was calculated as follows: ΔF/F=(F- Fbasal))/Fbackground
Judge's note: The page image on p9 shows one '(' and two ')' in the formula, and the word 'is'. The intended formula, (F-Fbasal)/Fbackground, is clear.
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Typo Misspelling: "Secondary andibodies used were donkey AlexaFluor" (antibodies).
- p. 10 Methods, Histology and immunofluorescence
Secondary andibodies used were donkey AlexaFluor
- p. 10 antibody list
Secondary andibodies used
Judge's note: Seen in the page image on p10.
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Typo Misspelling "hemotoxylin/eosin" in Methods (p10); the Figure 2 legend uses "Hematoxylin-eosin".
- p. 10 Methods, Histology
hemotoxylin/eosin or used for immunostaining
- p. 16 Figure 2 legend, panel j
Hematoxylin-eosin staining
- p. 10 Histology and immunofluorescence
hemotoxylin/eosin
Judge's note: The p10 crop shows 'hemotoxylin/eosin' and the p16 legend shows 'Hematoxylin-eosin'.
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Typo Number disagreement: "For immunohistochemistry, section were blocked" (sections were).
- p. 10 Methods, Histology and immunofluorescence
For immunohistochemistry, section were
Judge's note: Seen in the page image at the top of p10.
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Typo Methods (p11) print "Welcome Trust Sanger Institute"; the affiliations and acknowledgments spell it "Wellcome". Page 10 also prints "hemotoxylin/eosin" and "Secondary andibodies"
- p. 11 Methods, Research subject and gene identification
Welcome Trust Sanger Institute
- p. 10 Histology
hemotoxylin/eosin
- p. 10 Histology
Secondary andibodies
Judge's note: The page images show 'Welcome Trust Sanger Institute' on p11, 'hemotoxylin/eosin' at the top of p10 and 'Secondary andibodies' on p10. The affiliation on p1 and the acknowledgments use 'Wellcome'. These are plain misspellings.
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Typo Figure 6a legend (p20) prints "Saggital T1 (left) and axial T2 (right) images"; it should read 'Sagittal'
- p. 20 Figure 6 legend, panel a
Saggital T1 (left)
- p. 10 Histology
hemotoxylin/eosin
- p. 10 Immunofluorescence
Secondary andibodies
- p. 20 Fig 6a legend
Saggital T1
Judge's note: The p20 image shows 'Saggital'. The 'hemotoxylin' and 'andibodies' items also listed in this cluster are confirmed under C017 (p10).
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Typo Methods (p11): "DNA was sheared to 150bp lengths by sonification (Covaris...)"; the intended word is 'sonication'
- p. 11 Methods, Research subject and gene identification
DNA was sheared to 150bp lengths by sonification
Judge's note: The page image (C016-a/C017-a crops of p11) shows 'sonification'. Covaris shearing is done by sonication.
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Typo Reference 46 title is printed "A novel nonsense CDK5RAP2mutation in a Somali child", with the space missing
- p. 14 Reference 46
A novel nonsense CDK5RAP2mutation
Judge's note: The p14 image shows 'CDK5RAP2mutation' run together.
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Typo Figure 2 legend (p16) prints "c,-i, Staining for various brain region identities", with a stray comma in the panel range 'c–i'
- p. 16 Figure 2 legend
c,-i,
Judge's note: The p16 image shows the bold 'c,-i,' with a comma after c. Every other panel range in the legends is written without one.
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Typo Figure 6h legend (p21): "Control RGs at anaphase divided exclusively horizontal"; should read 'horizontally'
- p. 21 Figure 6h legend
divided exclusively horizontal
Judge's note: The p21 image shows 'divided exclusively horizontal'. This is a minor grammatical slip.
Second check: none (judge only)