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Record W3037404908 · doi:10.1101/2020.06.29.177709

<i>HLF</i> Expression Defines the Human Hematopoietic Stem Cell State

2020· preprint· en· W3037404908 on OpenAlexaff
Bernhard Lehnertz, Jalila Chagraoui, Tara MacRae, Elisa Tomellini, Sophie Corneau, Nadine Mayotte, Isabel Boivin, Guy Sauvageau

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldMedicine
TopicHematopoietic Stem Cell Transplantation
Canadian institutionsHôpital Maisonneuve-RosemontUniversité de MontréalInstitute for Research in Immunology and Cancer
Fundersnot available
KeywordsStem cellBiologyHaematopoiesisCord bloodEx vivoCell biologyTransplantationPopulationProgenitor cellBone marrowHematopoietic stem cellBlood cellImmunologyGeneticsIn vivoMedicine

Abstract

fetched live from OpenAlex

Abstract Hematopoietic stem cells (HSCs) sustain blood cell homeostasis throughout life and are able to regenerate all blood lineages following transplantation. Despite this clear functional definition, highly enriched isolation of human HSCs can currently only be achieved through combinatorial assessment of multiple surface antigens. While a number of transgenic HSC reporter mouse strains have been described, no analogous approach to prospectively isolate human HSCs has been reported. To identify genes with the most selective expression in human HSCs, we profiled population- and single-cell transcriptomes of fresh and ex vivo cultured cord blood derived HSPCs as well as peripheral blood, adult bone marrow and fetal liver. Based on these analyses, we propose the master transcription factor HLF ( Hepatic Leukemia Factor ) as one of the most specific HSC marker genes. To directly track its expression in human hematopoietic cells, we developed a genomic HLF reporter strategy, capable of selectively labeling the most immature blood cells on the basis of a single engineered parameter. Most importantly, HLF -expressing cells comprise all of the stem cell activity in culture and in vivo during serial transplantation. Taken together, these results experimentally establish HLF as a defining gene of the human hematopoietic stem cell state and outline a new approach to continuously mark these cells with high fidelity. Key Points In the human blood system, HLF expression is specific to stem cell populations in primary anatomical sites and during ex vivo expansion. CRISPR/rAAV6-mediated integration of a genomic HLF -reporter allows selective and stable genetic labeling of human HSCs ex vivo and in vivo .

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

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)0.0010.001

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 head0.023
GPT teacher head0.238
Teacher spread0.215 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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

Citations2
Published2020
Admission routes1
Has abstractyes

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