Overexpression of Jagged-1 and Its Intracellular Domain in Human Mesenchymal Stromal Cells Differentially Affect the Interaction with Hematopoietic Stem and Progenitor Cells
Bibliographic record
Abstract
Mesenchymal stromal cells (MSC) are an important component of the bone marrow microenvironment. Notch ligands expressed by MSC are known to play a regulatory role for hematopoietic stem and progenitor cells (HSPC) and in support of bone marrow homeostasis. While the role of Notch signaling in HSPC, their progeny, and MSC has been relatively well studied, little is known about the Notch-independent regulatory impact of Notch ligands on MSC themselves. In the present study, we used genetically engineered bone marrow-derived human MSC to study the function role of Jagged-1 and the Jagged-1 intracellular domain (JICD) with regard to the interaction with HSPC. We demonstrate that Jagged-1 in human MSC undergoes cleavage to produce an intracellular domain that translocates into the nucleus. JICD but not Jagged-1 overexpression was associated with an increased expression of stromal cell-derived factor-1. Short-term co-culture (7 days) of HSPC with JICD-overexpressing MSC, but not with Jagged-1-overexpressing MSC, led to increased proliferation of CD34(+) progenitors. In contrast, long-term co-culture of HSPC with Jagged-1-overexpressing MSC (up to 6 weeks) led to a significantly better support of cobblestone area-forming cells and long-term culture-initiating cells (LTC-ICs) compared with JICD-overexpressing MSC. Taken together, results of this study indicate that full-length Jagged-1 and JICD have differential effects on MSC and on their interaction with HSPC ex-vivo. JICD-overexpressing MSC induce proliferation of HSPCs in short-term culture at the expense of immature precursors (LTC-ICs), whereas Jagged-1 overexpressing MSC favor LTC-IC formation.
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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".