Abstract
Suppressor of cytokine signaling 3 (SOCS3) plays an important role in mice fetal liver erythropoiesis, but the roles of SOCS3 in human hematopoietic stem cells (HSCs) have not been well investigated. In the present study, lentiviral small interference RNA expression vectors (shRNA) of SOCS3 were constructed and stably transferred into HSCs. We found that SOCS3 knockdown induced erythroid expansion in HSCs. Conversely, Ectopic expression of SOCS3 in progenitor cells blocked erythroid expansion and erythroid colony formation of HSCs. To further explore the involved mechanism, we compared gene expression profiles of SOCS3-shRNA tranduced HSCs with that of control HSCs by whole genome microarrays. The results indicated that cell developmental process related genes, especially hematopoietic lineage-specific genes, associated with the responses to SOCS3 in HSCs.Downexpression of SOCS3 in HSCs or differentiated erythroid progenitor cells induced a transcriptional program enriched for erythroid development relative genes. Our results proved that SOCS3 down-expression induced lineage commitment towards erythroid progenitor cell fate by activation of erythroid-specific gene in HSCs and provided new insight into the mechanism of erythropoietic development.
Highlights
The availability of red blood cells (RBCs) transfusion is limited by both quantity and the risk of disease [1]
green fluorescent protein (GFP) +hematopoietic stem cells (HSCs) were sorted by fluorescence-activated cell sorting (Fig 1A and 1B) After sorting, the expression of Suppressor of cytokine signaling 3 (SOCS3) in HSCs were examined by real-time PCR and western–blot
CD34+ cells were seeded in methylcellulose. 14 day after seeding, we found shcontro1 CD34+ cells could form various types of hematopoietic colonies including colony-forming units–granulocyte-macrophage (CFU-GM), colony-forming units-macrophage (CFU-M) and burst forming unit erythroid (BFU-E) colonies
Summary
The availability of red blood cells (RBCs) transfusion is limited by both quantity and the risk of disease [1]. With the repaid development of biology research, generation of RBCs from HSCs and embryonic stem cells (ESCs) may represent an important new resource for blood transfusion [2,3,4,5,6]. It has great value to establish efficient ways for production RBCs in vitro and study the mechanism in erythropoietic development. Erythropoiesis is the process by which hematopoietic stem/progenitor cells give rise to lineage-committed erythroid precursors, and terminally differentiate into mature circulating red PLOS ONE | DOI:10.1371/journal.pone.0135259. Function of Socs-3 in Erythropoiesis blood cells. Erythropoiesis is controlled by cytokines in micro-environment and a lot of genes in cells [7,8,9]
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