Podocalyxin Is a Selective Marker of Erythroid Progenitors but Is Dispensable for Anemia Recovery.
Bibliographic record
Abstract
Abstract Podocalyxin, a member of the CD34-family of anti-adhesins, is induced on erythroid cells in the spleen and bone marrow following administration of high concentrations of erythropoietin (Epo), or, phenylhydrazine (PHz)-induced anemia. Notably, Podocalyxin is not expressed on committed erythroid progenitors during homeostatic red cell turnover. Our previous work has suggested that stress erythropoiesis in the mouse draws on a specific population of resident splenic erythroid progenitors which respond to a distinct set of signals during anemic recovery in contrast to the erythroid populations residing primarily in the marrow responsible for maintaining normal homeostasis (Lenox et al., 2005, Blood; Perry et al., 2007, Blood). During stress erythropoiesis, Podocalyxin expression is upregulated, in part, via a Stat5-dependent pathway in response to Epo (Sathyanarayana et al., 2007, Blood) and Podocalyxin expression has been postulated to play a key role in the release of reticulocytes into the periphery. In this work, we have addressed this hypothesis and further characterized the expression pattern of Podocalyxin during stress erythropoiesis. Since Podocalyxin (Podxl) gene deletion results in perinatal lethality (Doyonnas et al., 2001, J. Exp. Med), we used hematopoietic cell-reconstituted chimeric mice lacking Podocalyxin expression in their hematopoietic compartment. Ten weeks after transplantation, chimeric mice were demonstrated to have normal peripheral blood red cell and platelet homeostasis. Chimeric mice were subjected to Epo stimulation or chemically-induced models of anemia. We found that during stress erythropoiesis, Podocalyxin is rapidly upregulated on early erythroid precursors, with expression on populations with BFU-e and CFU-e, although not CFU-GM, potential. Podocalyxin expression continues through a proerythroblast stage of erythroid development and is maintained on immature reticulocytes in the periphery. While Podocalyxin is highly expressed on erythroblasts and progenitors during anemic stress recovery, we found that loss of Podocalyxin has no major influence on the proportion of erythroid progenitors and staged erythroblasts in the spleen and marrow in response to Epo and, further, Podocalyxin is dispensable for efficient recovery from chemically-induced models of anemia. Our findings suggest that Podocalyxin expression is not critical for reticulocyte release or efficient stress erythroid differentiation. We speculate that Podocalyxin may play a subtle role in early erythroid development during anemic recovery, population of bone marrow and spleen during late embryonic development or establishment of neo-natal homeostasis. Furthermore, we suggest Podocalyxin may be used as a highly specific marker to sort stress-induced BFU-e and CFU-e progenitors from lineage-marker depleted bone marrow, spleen or peripheral blood. MRH and SM contributed equally to this work and are fellows of the Strategic Training Program in Transfusion Science funded by the Canadian Institutes for Health Research (CIHR) and the Heart and Stroke Foundation of Canada at the University of British Columbia Centre for Blood Research(CBR). RFP holds a research grant from the National Blood Foundation(USA). KMM is a Michael Smith Foundation for Health Research Scholar and CBR Member.
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 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".