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Record W4283162937 · doi:10.1038/s41556-022-00931-x

Hyaluronic acid–GPRC5C signalling promotes dormancy in haematopoietic stem cells

2022· article· en· W4283162937 on OpenAlexaff
Yu Wei Zhang, Julian Mess, Nadim Aizarani, Pankaj Mishra, Carys Johnson, Mari Carmen Romero-Mulero, Jasmin Rettkowski, Katharina Schönberger, Nadine Obier, Karin Jäcklein, Nadine M. Woessner, Maria‐Eleni Lalioti, Talía Velasco-Hernández, Katarzyna Sikora, Ralph Wäsch, Bernhard Lehnertz, Guy Sauvageau, Thomas Manke, Pablo Menéndez, Sebastian G. Walter, Susana Minguet, Elisa Laurenti, Stefan Günther, Dominic Grün, Nina Cabezas‐Wallscheid

Bibliographic record

VenueNature Cell Biology · 2022
Typearticle
Languageen
FieldMedicine
TopicHematopoietic Stem Cell Transplantation
Canadian institutionsUniversité de MontréalInstitute for Research in Immunology and Cancer
FundersMedical Research CouncilBiotechnology and Biological Sciences Research CouncilJosé Carreras Leukämie-StiftungH2020 Marie Skłodowska-Curie ActionsMinisterio de Economía y CompetitividadGeneralitat de CatalunyaWellcome TrustBIRAXMax-Planck-GesellschaftDeutsche ForschungsgemeinschaftCentres de Recerca de CatalunyaEuropean CommissionRoyal SocietyEuropean Hematology Association
KeywordsHaematopoiesisStem cellDormancyBiologyCell biologyBone marrowImmunologyBotany

Abstract

fetched live from OpenAlex

Bone marrow haematopoietic stem cells (HSCs) are vital for lifelong maintenance of healthy haematopoiesis. In inbred mice housed in gnotobiotic facilities, the top of the haematopoietic hierarchy is occupied by dormant HSCs, which reversibly exit quiescence during stress. Whether HSC dormancy exists in humans remains debatable. Here, using single-cell RNA sequencing, we show a continuous landscape of highly purified human bone marrow HSCs displaying varying degrees of dormancy. We identify the orphan receptor GPRC5C, which enriches for dormant human HSCs. GPRC5C is also essential for HSC function, as demonstrated by genetic loss- and gain-of-function analyses. Through structural modelling and biochemical assays, we show that hyaluronic acid, a bone marrow extracellular matrix component, preserves dormancy through GPRC5C. We identify the hyaluronic acid-GPRC5C signalling axis controlling the state of dormancy in mouse and human HSCs.

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)0.001
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 score0.011
Threshold uncertainty score0.936

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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 integrity0.0000.002
Insufficient payload (model declined to judge)0.0010.000

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 head0.011
GPT teacher head0.255
Teacher spread0.244 · 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

Citations67
Published2022
Admission routes1
Has abstractyes

Explore more

Same venueNature Cell BiologySame topicHematopoietic Stem Cell TransplantationFrench-language works237,207