Podocalyxin Is a Selective Marker of Erythroid Progenitors but Is Dispensable for Anemia Recovery.
Notice bibliographique
Résumé
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.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
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| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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