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Record W4294119740 · doi:10.1016/j.stem.2022.08.001

Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells

2022· article· en· W4294119740 on OpenAlex
Thi Xuan Ai Pham, Amitesh Panda, Harunobu Kagawa, San Kit To, Cankat Ertekin, Grigorios Georgolopoulos, Sam Samuel Franciscus Allegonda van Knippenberg, Ryan Allsop, Alexandre Bruneau, Jonathan Sai‐Hong Chui, Lotte Vanheer, Adrian Janiszewski, Joel Chappell, Michael Oberhuemer, Raissa Songwa Tchinda, Irene Talón, Sherif Khodeer, Janet Rossant, Frederic Lluı́s, Laurent David, Nicolas Rivron, Bradley P. Balaton, Vincent Pasque

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueCell stem cell · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPluripotent Stem Cells Research
Canadian institutionsHospital for Sick Children
FundersEuropean Research CouncilHorizon 2020 Framework ProgrammeHorizon 2020KU LeuvenFonds Wetenschappelijk OnderzoekEuropean Resuscitation CouncilÖsterreichischen Akademie der WissenschaftenH2020 European Research CouncilAgence Nationale de la Recherche
KeywordsMesodermBiologyEpiblastGastrulationCell biologySomitogenesisGerm layerNODALInduced pluripotent stem cellNodal signalingEctodermTranscriptomeBrachyuryEmbryoid bodyEmbryonic stem cellEmbryogenesisEmbryoGeneticsGene expressionSomiteGene

Abstract

fetched live from OpenAlex

A hallmark of primate postimplantation embryogenesis is the specification of extraembryonic mesoderm (EXM) before gastrulation, in contrast to rodents where this tissue is formed only after gastrulation. Here, we discover that naive human pluripotent stem cells (hPSCs) are competent to differentiate into EXM cells (EXMCs). EXMCs are specified by inhibition of Nodal signaling and GSK3B, are maintained by mTOR and BMP4 signaling activity, and their transcriptome and epigenome closely resemble that of human and monkey embryo EXM. EXMCs are mesenchymal, can arise from an epiblast intermediate, and are capable of self-renewal. Thus, EXMCs arising via primate-specific specification between implantation and gastrulation can be modeled in vitro. We also find that most of the rare off-target cells within human blastoids formed by triple inhibition (Kagawa et al., 2021) correspond to EXMCs. Our study impacts our ability to model and study the molecular mechanisms of early human embryogenesis and related defects.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.120
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0010.002
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.029
GPT teacher head0.258
Teacher spread0.228 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it