Reversible switching of expression of c-kit and Pax-5 in immature hematopoietic progenitor cells by stromal cells

Tadashi Okubo, Nobuaki Yanai, Shuntaro Ikawa, Masuo Obinata

研究成果: Article査読

8 被引用数 (Scopus)

抄録

Objective. Bone marrow stromal cells provide the microenvironment for self-renewal and differentiation of hematopoietic stem/progenitor cells through complex cell-cell interaction. To elucidate the regulatory mechanisms of hematopoiesis by stromal cells, we established a novel stroma-dependent hematopoietic cell line and explored the phenotypic changes regulated by the two stromal cells. Materials and Methods. DFC-28 cells clonally established from long-term bone marrow culture of C57BL/6 mice were sustained by coculture on MSS62 cells (mouse spleen stromal cell line). When DFC-28 cells were transferred to TBR31-1 cells (mouse bone marrow stromal cell line), their phenotypic changes were analyzed by flow cytometry and reverse transcriptase polymerase chain reaction. Results. DFC-28 cells on MSS62 cells exhibited surface phenotypes of the immature hematopoietic progenitor cells (Lin-AA4.1+c-kit+Sca-1-). By stroma-replacement from MSS62 cells to TBR31-1 cells, DFC-28 cells were differentiated into very early B-lymphoid stage characterized by c-kit down-regulation and induction of BP-1 and B-lymphoid-associated genes (Pax-5, CD19, TdT, Rag-1, and Rag-2). In addition, the differentiation phenotypes reverted to the immature state characterized by c-kit induction and down-regulation of BP-1 and B-lymphoid-associated genes by replacing stroma back to MSS62 from TBR31-1. Interleukin-7 stimulation and conditioned medium of TBR31-1 cells were ineffective in converting the differentiation phenotypes of DFC-28 cells. Conclusion. The results demonstrate that the differentiation phenotypes and growth potential of stroma-dependent hematopoietic progenitor cells we established could be reversibly controlled via direct contact with stromal cells in the microenvironment.

本文言語English
ページ(範囲)1193-1201
ページ数9
ジャーナルExperimental Hematology
30
10
DOI
出版ステータスPublished - 2002 10 1

ASJC Scopus subject areas

  • 分子生物学
  • 血液学
  • 遺伝学
  • 細胞生物学
  • 癌研究

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