Identification of key genes responsible for cytokine-induced erythroid and myeloid differentiation and switching of hematopoietic stem cells by RAGE.
We utilized a unique culture system to analyze the expression patterns of gene, protein, and cell surface antigen, and the biological process of the related genes in erythroid and myeloid differentiation and switching of hematopoietic stem cells (HSCs) in response to cytokine alterations. Gene-specific fragments (266) identified from five populations of cytokine-stimulated HSCs were categorized into three groups: (1) expressed specifically in a single cell population; (2) expressed in two cell populations, and (3) expressed in three or more populations. Of 145 defined cDNAs, three (2%) were novel genes. Protein two-dimensional gel electrophoresis and flow cytometry analyses showed overlapped and distinguished protein expression profiles in the cell populations studied. Biological process mapping of mRNAs expressed in erythroid and myeloid lineages indicated that mRNAs shared by both lineages attended 'core processes,' whereas genes specifically expressed in either lineage alone were related to specific processes or cellular maturation. Data from this study support the hypothesis that committed HSCs (E14 or G14) cells can still be redirected to develop into myeloid or erythroid cells when erythropoietin (EPO) is replaced with granulocyte-colony stimulating factor (G-CSF) under erythroid-cultured condition or G-CSF with EPO in myeloid-cultured environment, respectively. Our results suggest that genes or proteins co-expressed in erythroid and myeloid lineages may be essential for the lineage maintenance and switching in hematopoiesis.
Chen
Ling
L
Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Zhang
Hong
H
Shi
Ying
Y
Chin
Kyung L
KL
Tang
Delia C
DC
Rodgers
Griffin P
GP
D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D004921:Erythropoietin / Q000502:physiology; D020869:Gene Expression Profiling; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism
D016207:Cytokines; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor