NDLI: Biochemical measurements on single erythroid progenitor cells shed light on the combinatorial regulation of red blood cell production

Content Provider	Royal Society of Chemistry (RSC)
Author	Wang, Weijia Audet, Julie Akbarian, Vahe
Copyright Year	2013
Abstract	Adult bone marrow (BM) erythrocyte colony-forming units (CFU-Es) are important cellular targets for the treatment of anemia and also for the manufacture of red blood cells (RBCs) ex vivo. We obtained quantitative biochemical measurements from single and small numbers of CFU-Es by isolating and analyzing c-Kit+CD71highTer119− cells from adult mouse BM and this allowed us to identify two mechanisms that can be manipulated to increase RBC production. As expected, maximum RBC output was obtained when CFU-Es were stimulated with a combination of Stem Cell Factor (SCF) and Erythropoietin (EPO) mainly because SCF supports a transient CFU-E expansion and EPO promotes the survival and terminal differentiation of erythroid progenitors. However, we found that one of the main factors limiting the output in RBCs was that EPO induces a downregulation of c-Kit expression which limits the transient expansion of CFU-Es. In the presence of SCF, the EPO-mediated downregulation of c-Kit on CFU-Es is delayed but still significant. Moreover, treatment of CFU-Es with 1-Naphthyl PP1 could partially inhibit the downregulation of c-Kit induced by EPO, suggesting that this process is dependent on a Src family kinase, v-Src and/or c-Fyn. We also found that CFU-E survival and proliferation was dependent on the level of time-integrated extracellular-regulated kinase (ERK) activation in these cells, all of which could be significantly increased when SCF and EPO were combined with mouse fetal liver-derived factors. Taken together, these results suggest two novel molecular strategies to increase RBC production and regeneration.
Starting Page	234
Ending Page	245
Page Count	12
File Format	HTM / HTML PDF
ISSN	1742206X
Volume Number	9
Issue Number	2
Journal	Molecular BioSystems
DOI	10.1039/c2mb25348h
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Erythropoietin Anemia Src family kinase Red blood cell Mitogen-activated protein kinase RBC Mouse Kinase SCF Bone marrow CD117 CFU-E V-Src
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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