Smad7 alters cell fate decisions of human hematopoietic repopulating cells
Bibliographic record
Abstract
Intracellular Smad proteins mediate signal transduction of the transforming growth factor-beta (TGF-beta) superfamily that play pleiotropic roles in hematopoietic development, suggesting that intracellular Smad proteins may play key roles in hematopoietic regulation. Although inhibitory Smad7, which negatively regulates TGF-beta signaling, has been implicated in the development of mature hematopoietic cells, a role for Smad7 in regulating more primitive hematopoietic cells has yet to be examined. Here, Smad7 was overexpressed in primary human severe combined immunodeficient (SCID) repopulating cells (SRCs), representing a common myeloid/lymphoid precursor cell with the functional capacity to repopulate the bone marrow of nonobese diabetic (NOD)/SCID recipient mice. Retroviral transduction of Smad7 into human umbilical cord blood (CB)-SRCs caused a shift from lymphoid dominant engraftment toward increased myeloid contribution, and increased the myeloid-committed clonogenic progenitor frequency in reconstituted mice. Neither myeloid nor B-lymphoid lineage developmental stages were compromised by Smad7 overexpression, suggesting Smad7 regulates cell fate commitment decisions of myeloid/lymphoid precursors by augmenting myeloid differentiation at the expense of lymphoid commitment. In addition, global gene expression analysis using microarray was used to identify potential target genes regulated by Smad7 in primitive hematopoietic cells that may control this process. Our study demonstrates a novel and unexpected role for Smad7 in modulating the cell fate decisions of primary multipotent human repopulating cells and establishes a role for Smad7 in the development of primitive human hematopoietic cells.
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) | 0.000 | 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) | 0.002 | 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".