Evidence map›Paper›PMID 34142711›Full record

ArticleDevelopment (Cambridge, England)2021

Axial elongation of caudalized human organoids mimics aspects of neural tube development.

Ashley R G Libby, David A Joy, Nicholas H Elder, Emily A Bulger, Martina Z Krakora, Eliza A Gaylord, Frederico Mendoza-Camacho, Jessica C Butts, Todd C McDevitt

Open access · bronzeAbstract read
In one paragraph

Article in Development (Cambridge, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Ashley R G LibbyDevelopmental and Stem Cell Biology PhD Program, University of California, San Francisco, CA 94143, USA.ORCID 0000-0002-8139-8844
David A JoyGladstone Institutes, San Francisco, CA 94158, USA.ORCID 0000-0001-9941-9538
Nicholas H ElderDevelopmental and Stem Cell Biology PhD Program, University of California, San Francisco, CA 94143, USA.ORCID 0000-0003-0889-7687
Emily A BulgerDevelopmental and Stem Cell Biology PhD Program, University of California, San Francisco, CA 94143, USA.ORCID 0000-0003-2967-1994
Martina Z KrakoraGladstone Institutes, San Francisco, CA 94158, USA.
Eliza A GaylordDevelopmental and Stem Cell Biology PhD Program, University of California, San Francisco, CA 94143, USA.
Frederico Mendoza-CamachoDevelopmental and Stem Cell Biology PhD Program, University of California, San Francisco, CA 94143, USA.
Jessica C ButtsGladstone Institutes, San Francisco, CA 94158, USA.
Todd C McDevittGladstone Institutes, San Francisco, CA 94158, USA.ORCID 0000-0002-8905-4931
Gladstone Institutes · USUniversity of California, San Francisco · US

Funding

PREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7M
Genetically inducible cell sorting to interrogate human pluripotent stem cell lineage transitionsF31HL140907 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIBBY, ASHLEY · 2018 to 2019
$71k
NHLBI NIH HHS F31 HL140907NICHD NIH HHS T32 HD007470
6 · The paper itself

Abstract

Axial elongation of the neural tube is crucial during mammalian embryogenesis for anterior-posterior body axis establishment and subsequent spinal cord development, but these processes cannot be interrogated directly in humans as they occur post-implantation. Here, we report an organoid model of neural tube extension derived from human pluripotent stem cell (hPSC) aggregates that have been caudalized with Wnt agonism, enabling them to recapitulate aspects of the morphological and temporal gene expression patterns of neural tube development. Elongating organoids consist largely of neuroepithelial compartments and contain TBXT+SOX2+ neuro-mesodermal progenitors in addition to PAX6+NES+ neural progenitors. A critical threshold of Wnt agonism stimulated singular axial extensions while maintaining multiple cell lineages, such that organoids displayed regionalized anterior-to-posterior HOX gene expression with hindbrain (HOXB1) regions spatially distinct from brachial (HOXC6) and thoracic (HOXB9) regions. CRISPR interference-mediated silencing of TBXT, a Wnt pathway target, increased neuroepithelial compartmentalization, abrogated HOX expression and disrupted uniaxial elongation. Together, these results demonstrate the potent capacity of caudalized hPSC organoids to undergo axial elongation in a manner that can be used to dissect the cellular organization and patterning decisions that dictate early human nervous system development.

Indexed as

Body PatterningOrganogenesisOrganoidsCell DifferentiationEmbryonic DevelopmentGene Expression Regulation, DevelopmentalHumansMesodermNeural TubeNeurogenesisPluripotent Stem CellsWnt Signaling PathwayNeural tube developmentOrganoid modelsStem cell biology

Identifiers

PMID34142711
PMCPMC8254868
OpenAlexW3170776054

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.