Resolution of pluripotential intermediates in murine hematopoietic differentiation by global complementary DNA amplification from single cells: confirmation of assignments by expression profiling of cytokine receptor transcripts
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Bibliographic record
Abstract
Although hematopoiesis is known to proceed from stem cells through a graded series of multipotent, oligopotent, and unipotent precursor cells, it has been difficult to resolve these cells physically one from another. There is, therefore, corresponding uncertainty about the exact distribution and timing of the expression of genes known to be important in hematopoietic differentiation. In earlier work, the generation of a set of amplified complementary DNAs (cDNAs) from single precursor cells was described, whose biologic potential was determined by the outcome of cultured sibling cells. In this study, the new acquisition of cDNA from multipotent myeloid precursor cells is described, as is the mapping of RNA-level expression of 17 distinct cytokine receptors (c-kit, Flk-1, Flk-2/Flt-3, c-fms, gp130, erythropoietin receptor, GM-CSFRalpha, G-CSFR, TNFR1, IL-1RI, IL-1RII, IL-2Rbeta, IL-3-specific beta receptor, IL-4R, IL-6Ralpha, IL-7Ralpha, and IL-11Ralpha) to the enlarged sample set, spanning stages from pentapotent precursors through oligopotent intermediates to committed and maturing cells in the myeloid and lymphoid lineages. Although the enhanced scope and resolving power of the analysis yielded previously unreported observations, there was overall agreement with known biologic responsiveness at individual stages, and major contradictions did not arise. Moreover, each precursor category displayed a unique overall pattern of hybridization to the matrix of 17 receptor probes, supporting the notion that each sample pool indeed reflected a unique precursor stage. Collectively, the results provide supportive evidence for the validity of the cDNA assignments to particular stages, the depth of the information captured, and the unique capacity of the sample matrix to resolve individual stages in the hematopoietic hierarchy.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 it