title: During EPO or anemia challenge, erythroid progenitor cells transit through a selectively expandable proerythroblast pool.
abstract: Investigations of bone marrow (BM) erythroblast development are important for clinical concerns but are hindered by progenitor cell and tissue availability. We therefore sought to more specifically define dynamics, and key regulators, of the formation of developing BM erythroid cell cohorts. A unique Kit(-)CD71(high)Ter119(-) "stage E2" proerythroblast pool first is described, which (unlike its Kit(+) "stage E1" progenitors, or maturing Ter119(+) "stage E3" progeny) proved to selectively expand ∼ 7-fold on erythropoietin challenge. During short-term BM transplantation, stage E2 proerythroblasts additionally proved to be a predominantly expanded progenitor pool within spleen. This E1→E2→E3 erythroid series reproducibly formed ex vivo, enabling further characterizations. Expansion, in part, involved E1 cell hyperproliferation together with rapid E2 conversion plus E2 stage restricted BCL2 expression. Possible erythropoietin/erythropoietin receptor proerythroblast stage specific events were further investigated in mice expressing minimal erythropoietin receptor alleles. For a hypomorphic erythropoietin receptor-HM allele, major defects in erythroblast development occurred selectively at stage E2. In addition, stage E2 cells proved to interact productively with primary BM stromal cells in ways that enhanced both survival and late-stage development. Overall, findings reveal a novel transitional proerythroblast compartment that deploys unique expansion devices.
authors.affiliation: COBRE Center of Excellence in Stem Cell Biology and Regenerative Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Dev
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.forename: Pradeep
authors.initials: P
authors.lastname: Sathyanarayana
authors.forename: Anamika
authors.initials: A
authors.lastname: Pradeep
authors.forename: Christine
authors.initials: C
authors.lastname: Emerson
authors.forename: Don M
authors.initials: DM
authors.lastname: Wojchowski
mesh_terms: D000483:Alleles; D000740:Anemia; D000818:Animals; D016026:Bone Marrow Transplantation; D002450:Cell Communication / Q000502:physiology; D049109:Cell Proliferation; D004900:Erythroblasts / Q000166:cytology*; D015672:Erythroid Precursor Cells / Q000166:cytology*; D004920:Erythropoiesis; D004921:Erythropoietin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017467:Receptors, Erythropoietin / Q000235:genetics; D013154:Spleen / Q000166:cytology; D017154:Stromal Cells
chemical_list: D017467:Receptors, Erythropoietin; D004921:Erythropoietin
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