Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells
Bibliographic record
Abstract
BACKGROUND: Hematopoietic stem cells (HSCs) or repopulating cells are able to self-renew and differentiate into cells of all hematopoietic lineages, and they can be enriched using the CD34 cell surface marker. Because of this unique property, HSCs have been used for HSC transplantation and gene therapy applications. However, the inability to expand HSCs has been a significant limitation for clinical applications. Here we examine, in a clinically relevant nonhuman primate model, the ability of HOXB4 to expand HSCs to potentially overcome this limitation. METHODS AND FINDINGS: Using a competitive repopulation assay, we directly compared in six animals engraftment of HOXB4GFP (HOXB4 green fluorescent protein) and control (yellow fluorescent protein [YFP])-transduced and expanded CD34+ cells. In three animals, cells were infused after a 3-d transduction culture, while in three other animals cells were infused after an additional 6-9 d of ex vivo expansion. We demonstrate that HOXB4 overexpression resulted in superior engraftment in all animals. The most dramatic effect of HOXB4 was observed early after transplantation, resulting in an up to 56-fold higher engraftment compared to the control cells. At 6 mo after transplantation, the proportion of marker gene-expressing cells in peripheral blood was still up to 5-fold higher for HOXB4GFP compared to YFP-transduced cells. CONCLUSIONS: These data demonstrate that HOXB4 overexpression in CD34+ cells has a dramatic effect on expansion and engraftment of short-term repopulating cells and a significant, but less pronounced, effect on long-term repopulating cells. These data should have important implications for the expansion and transplantation of HSCs, in particular for cord blood transplantations where often only suboptimal numbers of HSCs are available.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
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".