Graft-versus-Host Disease Causes Broad Suppression of Hematopoietic Primitive Cells and Blocks Megakaryocyte Differentiation in a Murine Model
Bibliographic record
Abstract
Cytopenia and delayed immune reconstitution with acute graft-versus-host disease (aGVHD) indicate a poor prognosis. However, how donor-derived cell hematopoiesis is impaired in aGVHD is not well understood. We addressed this issue by studying the kinetics of hematopoiesis and the functions of hematopoietic stem and progenitor cells in an aGVHD model with haplo-MHC-matched murine bone marrow transplantation. Although hematopoiesis was progressively suppressed during aGVHD, the hematopoietic regenerative potential of donor-derived hematopoietic stem cells remains intact. There was a dramatic reduction in primitive hematopoietic cells and a defect in the ability of these cells to generate common myeloid progenitors (CMPs) and megakaryocyte/erythrocyte progenitors (MEPs). These effects were observed along with a concomitant increase in granulocyte/macrophage progenitors, suggesting that differentiation into MEPs is blocked during aGVHD. Interestingly, cyclosporine A was able to partially reverse the hematopoietic suppression as well as the differentiation blockage of CMPs. These data provide new insights into the pathogenesis of aGVHD and may improve the clinical management of aGVHD.
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 imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".