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Record W4391931733 · doi:10.1038/s41592-024-02172-2

Generation of complex bone marrow organoids from human induced pluripotent stem cells

2024· article· en· W4391931733 on OpenAlex
Stephanie Frenz-Wiessner, Savannah Fairley, Maximilian Buser, Isabel Goek, Kirill Salewskij, Gustav Jonsson, David W. Illig, Benedicta zu Putlitz, Daniel Petersheim, Yue Li, Pin‐Hsuan Chen, Martina Kalauz, Raffaele Conca, Michael Sterr, Johanna Geuder, Yoko Mizoguchi, Remco T. A. Megens, Monika I. Linder, Daniel Kotlarz, Martina Rudelius, Josef Penninger, Carsten Marr, Christoph Klein

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

VenueNature Methods · 2024
Typearticle
Languageen
FieldMedicine
TopicMesenchymal stem cell research
Canadian institutionsUniversity of British Columbia
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesHector StiftungMedizinische Universität WienUniversität WienBundesministerium für Bildung und ForschungLudwig-Maximilians-Universität MünchenDeutsche ForschungsgemeinschaftFondation LeducqEuropean CommissionBundesministerium für Bildung, Wissenschaft und ForschungDeutsches Zentrum für InfektionsforschungElse Kröner-Fresenius-StiftungLeona M. and Harry B. Helmsley Charitable TrustÖsterreichischen Akademie der WissenschaftenEuropean Federation of Pharmaceutical Industries and AssociationsU.S. Department of Health and Human Services
KeywordsOrganoidInduced pluripotent stem cellStem cellCell biologyBone marrowHuman boneBiologyHuman Induced Pluripotent Stem CellsComputational biologyEmbryonic stem cellImmunologyGeneticsGeneIn vitro

Abstract

fetched live from OpenAlex

The human bone marrow (BM) niche sustains hematopoiesis throughout life. We present a method for generating complex BM-like organoids (BMOs) from human induced pluripotent stem cells (iPSCs). BMOs consist of key cell types that self-organize into spatially defined three-dimensional structures mimicking cellular, structural and molecular characteristics of the hematopoietic microenvironment. Functional properties of BMOs include the presence of an in vivo-like vascular network, the presence of multipotent mesenchymal stem/progenitor cells, the support of neutrophil differentiation and responsiveness to inflammatory stimuli. Single-cell RNA sequencing revealed a heterocellular composition including the presence of a hematopoietic stem/progenitor (HSPC) cluster expressing genes of fetal HSCs. BMO-derived HSPCs also exhibited lymphoid potential and a subset demonstrated transient engraftment potential upon xenotransplantation in mice. We show that the BMOs could enable the modeling of hematopoietic developmental aspects and inborn errors of hematopoiesis, as shown for human VPS45 deficiency. Thus, iPSC-derived BMOs serve as a physiologically relevant in vitro model of the human BM microenvironment to study hematopoietic development and BM diseases.

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 categoriesInsufficient payload (model declined to judge)
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 score0.115
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.182
GPT teacher head0.457
Teacher spread0.275 · 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