title: Promotion of Erythropoietic Differentiation in Hematopoietic Stem Cells by SOCS3 Knock-Down.
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.
authors.affiliation: First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors.forename: Yu-xiao
authors.initials: YX
authors.lastname: Liu
authors.affiliation: Third Military Medical University, Chongqing, China; General Hospital of Beijing Military Command, Beijing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Dong
authors.affiliation: Beijing Institution of Transfusion Medicine, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gong
authors.affiliation: First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Su
authors.affiliation: Beijing Institution of Transfusion Medicine, Beijing, China.
authors.forename: Su-bo
authors.initials: SB
authors.lastname: Li
authors.affiliation: First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors.forename: Hai-tao
authors.initials: HT
authors.lastname: Zhang
authors.affiliation: First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors.forename: Jia-ling
authors.initials: JL
authors.lastname: Liu
authors.affiliation: First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors.forename: Jing-hui
authors.initials: JH
authors.lastname: Xue
authors.affiliation: Beijing Institution of Transfusion Medicine, Beijing, China.
authors.forename: Shou-ping
authors.initials: SP
authors.lastname: Ji
authors.affiliation: First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors.forename: Zhi-wen
authors.initials: ZW
authors.lastname: Zhang
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000166:cytology*; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D015894:Genome, Human; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006454:Hemoglobins / Q000737:chemistry; D006801:Humans; D016086:Lentivirus; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D018952:Antigens, CD34; D006454:Hemoglobins; D034741:RNA, Small Interfering; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins