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Record W4293063328 · doi:10.15252/embr.202255502

Identification and characterization of in vitro expanded hematopoietic stem cells

2022· article· en· W4293063328 on OpenAlexaff
L C James, Daniel Bode, Iwo Kuciński, Alyssa Cull, Fiona Bain, H. Becker, Maria Jassinskaja, Melania Barile, Grace Boyd, Miriam Belmonte, Andy G.X. Zeng, Kyomi J. Igarashi, Juan Rubio‐Lara, Mairi Shepherd, Anna Clay, John E. Dick, Adam C. Wilkinson, Hiromitsu Nakauchi, Satoshi Yamazaki, Berthold Göttgens, David G. Kent

Bibliographic record

VenueEMBO Reports · 2022
Typearticle
Languageen
FieldMedicine
TopicHematopoietic Stem Cell Transplantation
Canadian institutionsPrincess Margaret Cancer CentreUniversity of TorontoUniversity Health Network
FundersVetenskapsrådetCambridge Institute for Medical Research, University of CambridgeHORIZON EUROPE European Research CouncilBiotechnology and Biological Sciences Research CouncilMedical Research CouncilCancer Research UKUniversity of CambridgeNational Centre for the Replacement, Refinement and Reduction of Animals in ResearchNational Centre for the Replacement Refinement and Reduction of Animals in ResearchBlood Cancer UKNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchWellcome Trust
KeywordsBiologyclone (Java method)HaematopoiesisStem cellGene expression profilingComputational biologyCell biologyGeneTransplantationGeneticsGene expression

Abstract

fetched live from OpenAlex

Hematopoietic stem cells (HSCs) cultured outside the body are the fundamental component of a wide range of cellular and gene therapies. Recent efforts have achieved > 200-fold expansion of functional HSCs, but their molecular characterization has not been possible since the majority of cells are non-HSCs and single cell-initiated cultures have substantial clone-to-clone variability. Using the Fgd5 reporter mouse in combination with the EPCR surface marker, we report exclusive identification of HSCs from non-HSCs in expansion cultures. By directly linking single-clone functional transplantation data with single-clone gene expression profiling, we show that the molecular profile of expanded HSCs is similar to proliferating fetal HSCs and reveals a gene expression signature, including Esam, Prdm16, Fstl1, and Palld, that can identify functional HSCs from multiple cellular states. This "repopulation signature" (RepopSig) also enriches for HSCs in human datasets. Together, these findings demonstrate the power of integrating functional and molecular datasets to better derive meaningful gene signatures and opens the opportunity for a wide range of functional screening and molecular experiments previously not possible due to limited HSC numbers.

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.

How this classification was reachedexpand

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)0.000
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 score0.038
Threshold uncertainty score0.329

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
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 head0.013
GPT teacher head0.246
Teacher spread0.232 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations45
Published2022
Admission routes1
Has abstractyes

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Same venueEMBO ReportsSame topicHematopoietic Stem Cell TransplantationFrench-language works237,207