Frizzled-6 Regulates Hematopoietic Stem/Progenitor Cell Survival and Self-Renewal
Bibliographic record
Abstract
Adult hematopoietic stem/progenitor cell (HSPC) numbers remain stable in the absence of external stressors. After bone marrow (BM) transplant, HSPCs need to expand substantially to repopulate the BM and replenish the peripheral blood cell pool. In this study, we show that a noncanonical Wnt receptor, Frizzled-6 (Fzd6), regulates HSPC expansion and survival in a hematopoietic cell-intrinsic manner. Fzd6 deficiency increased the ratio of Flt3(hi) multipotent progenitors to CD150(+) stem cells in the mouse BM, suggesting defective stem cell maintenance. Competitive transplantation experiments demonstrated that Fzd6(-) (/) (-) HSPCs were able to home to the BM but were severely impaired in their capacity to reconstitute a lethally irradiated host. Lack of Fzd6 resulted in a strong activation of caspase-3 and a gradual loss of donor HSPCs and peripheral blood granulocytes. Fzd6 was also necessary for the efficient HSPC expansion during emergency hematopoiesis. Mechanistically, Fzd6 is a negative regulator of Cdc42 clustering in polarized cells. Furthermore, β-catenin-dependent signaling may be disinhibited in Fzd6(-) (/) (-) HSPCs. Collectively, our data reveal that Fzd6 has an essential role in HSPC maintenance and survival. Noncanonical Wnt-Fzd6 signaling pathway could thus present an interesting target for promoting HSPC expansion and multilineage hematopoietic recovery after transplant.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".