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Record W2171172082 · doi:10.1126/science.aab2116

Distinct routes of lineage development reshape the human blood hierarchy across ontogeny

2015· article· en· W2171172082 on OpenAlex
Faiyaz Notta, Sasan Zandi, Naoya Takayama, Stephanie M. Dobson, Olga I. Gan, Gavin W. Wilson, Kerstin B. Kaufmann, Jessica McLeod, Elisa Laurenti, Cyrille F. Dunant, John D. McPherson, Lincoln Stein, Yigal Dror, John E. Dick

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.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueScience · 2015
Typearticle
Languageen
FieldMedicine
TopicHematopoietic Stem Cell Transplantation
Canadian institutionsHospital for Sick ChildrenPrincess Margaret Cancer CentreOntario Institute for Cancer ResearchUniversity of TorontoUniversity Health Network
FundersOntario Ministry of Research and InnovationCanadian Institutes of Health ResearchOntario Ministry of Research, Innovation and ScienceTerry Fox FoundationCanadian Cancer SocietyWellcomeOntario Genomics InstituteAplastic Anemia and Myelodysplasia Association of CanadaOntario Institute for Cancer ResearchHospital for Sick ChildrenWellcome Trust
KeywordsProgenitor cellBiologyHaematopoiesisLineage (genetic)Stem cellMultipotent Stem CellProgenitorCell biologyImmunologyMyeloidGeneticsGene

Abstract

fetched live from OpenAlex

In a classical view of hematopoiesis, the various blood cell lineages arise via a hierarchical scheme starting with multipotent stem cells that become increasingly restricted in their differentiation potential through oligopotent and then unipotent progenitors. We developed a cell-sorting scheme to resolve myeloid (My), erythroid (Er), and megakaryocytic (Mk) fates from single CD34(+) cells and then mapped the progenitor hierarchy across human development. Fetal liver contained large numbers of distinct oligopotent progenitors with intermingled My, Er, and Mk fates. However, few oligopotent progenitor intermediates were present in the adult bone marrow. Instead, only two progenitor classes predominate, multipotent and unipotent, with Er-Mk lineages emerging from multipotent cells. The developmental shift to an adult "two-tier" hierarchy challenges current dogma and provides a revised framework to understand normal and disease states of human hematopoiesis.

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)0.002
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
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 score0.098
Threshold uncertainty score0.227

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.062
GPT teacher head0.347
Teacher spread0.285 · 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