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Influence of lineage‐specific cytokines on commitment and asymmetric cell division of haematopoietic progenitor cells
Author(s) -
Chen Ling,
Zhang Jiachang,
Tang Delia C.,
Fibach Eitan,
Rodgers Griffin P.
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03638.x
Subject(s) - haematopoiesis , biology , progenitor cell , cd34 , myeloid , population , erythropoietin , stem cell , microbiology and biotechnology , cell division , interleukin 3 , lineage markers , immunology , cell , t cell , antigen presenting cell , endocrinology , genetics , medicine , immune system , environmental health
Summary. We examined the influence of cytokines on erythroid‐ and myeloid‐lineage development of AC133 + cells during primary and secondary cultures. Cells cultured for 14 d in liquid medium containing erythropoietin (EPO) were amplified 831‐fold with 98·2% erythroid cells. A similar culture exposed to granulocyte colony‐stimulating factor (G‐CSF) grew 1350‐fold with 97·4% myeloid cells. To assess whether the cells with EPO inducement could respond at this point to G‐CSF signal, or vice versa, the EPO‐stimulated population was re‐grown with G‐CSF, constituting 95·2% myeloid, of 5075‐fold, cells after 14 d of re‐culture. Conversely, reculture of the G‐CSF‐stimulated population with EPO resulted in a 4083‐fold growth with 81·4% erythroid cells. Semisolid culture containing EPO orG‐CSF showed that some individual colonies had self‐ renewal potential after 14 d culture and could be induced todevelop into a different lineage. Analysis of primitive markers, CD34 and Notch1, or lineage markers, EPO‐R and CD13, by single‐cell reverse transcription polymerase chain reaction showed that individual colonies of 2–16 cells contained at least one CD34‐positive cell with expression ofNotch1 and co‐expression of EPO‐R and CD13 appeared on either CD34‐positive or CD34‐negative cells. In situ hybridization with the same cell surface markers in cell populations confirmed the asymmetric cell division and co‐expression from single cell data. The study provides a useful model for the analysis of multipotential progenitor development, and indicates that progenitor cells co‐express genes from different lineage pathways before commitment and that cytokines influence lineage commitment.