Podocalyxin selectively marks erythroid-committed progenitors during anemic stress but is dispensable for efficient recovery.
OBJECTIVE
Podocalyxin expression on Ter119(+) erythroblasts is induced following administration of erythropoietin (Epo) or phenylhydrazine treatment, but is notably absent on committed erythroid progenitors during homeostatic red cell turnover. Following high-dose Epo administration in vivo, podocalyxin surface expression is upregulated, in part, via a signal transducers and activators of transcription 5-dependent pathway and this expression has been postulated to play a role in the release of reticulocytes from hematopoietic organs into the periphery under conditions of increased erythropoietic rate. Here we have thoroughly addressed this hypothesis and further examined the expression profile of podocalyxin during Epo-induced erythroblast expansion and stress erythropoiesis.


METHODS
Following Epo induction, progenitor cells were sorted to characterize podocalyxin expression during stress. In addition, as podocalyxin-deficient mice die perinatally, we used chimeric mice reconstituted with wild-type or podocalyxin-deficient hematopoietic cells to analyze differences in response to high dose Epo administration and chemically induced anemia.


RESULTS
Podocalyxin surface expression is rapidly upregulated in response to stress and marks early erythroid progenitors and erythroblasts. Despite loss of podocalyxin, chimeras exhibit normal basal erythropoiesis and no differences in erythroid progenitor proportions in the spleen and marrow in response to Epo. Further, podocalyxin is dispensable for efficient recovery from models of anemia.


CONCLUSIONS
We demonstrate that podocalyxin is a highly specific marker of stress-induced blast-forming unit erythroid and colony-forming unit erythroid progenitors in mouse bone marrow and spleen. In addition, our findings suggest that podocalyxin is not necessary for efficient erythroblast expansion, erythroid differentiation, or reticulocyte release in response to Epo stimulation in vivo.
Maltby
Steven
S
The Biomedical Research Centre, The University of British Columbia, Vancouver, Canada.
Hughes
Michael R
MR
Zbytnuik
Lori
L
Paulson
Robert F
RF
McNagny
Kelly M
KM
D000740:Anemia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D016877:Oxidants / Q000633:toxicity; D010659:Phenylhydrazines / Q000633:toxicity; D012156:Reticulocytes / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics; D013154:Spleen / Q000378:metabolism; D013312:Stress, Physiological; D018183:Transplantation Chimera; D015854:Up-Regulation / Q000187:drug effects*
D000943:Antigens, Differentiation; D016877:Oxidants; D010659:Phenylhydrazines; D050799:STAT5 Transcription Factor; D012795:Sialoglycoproteins; C001643:podocalyxin; C030299:phenylhydrazine; D004921:Erythropoietin