Palacios R, Golunski E, Samaridis J
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7530-4. doi: 10.1073/pnas.92.16.7530.
Hematopoietic stem cells (HSC) are unique in that they give rise both to new stem cells (self-renewal) and to all blood cell types. The cellular and molecular events responsible for the formation of HSC remain unknown mainly because no system exists to study it. Embryonic stem (ES) cells were induced to differentiate by coculture with the stromal cell line RP010 and the combination of interleukin (IL) 3, IL-6, and F (cell-free supernatants from cultures of the FLS4.1 fetal liver stromal cell line). Cell cytometry analysis of the mononuclear cells produced in the cultures was consistent with the presence of PgP-1+ Lin- early hematopoietic (B-220- Mac-1- JORO 75- TER 119-) cells and of fewer B-220+ IgM- B-cell progenitors and JORO 75+ T-lymphocyte progenitors. The cell-sorter-purified PgP-1+ Lin- cells produced by induced ES cells could repopulate the lymphoid, myeloid, and erythroid lineages of irradiated mice. The ES-derived PgP-1+ Lin- cells must possess extensive self-renewal potential, as they were able to produce hematopoietic repopulation of secondary mice recipients. Indeed, marrow cells from irradiated mice reconstituted (15-18 weeks before) with PgP-1+ Lin- cell-sorter-purified cells generated by induced ES cells repopulated the lymphoid, myeloid, and erythroid lineages of secondary mouse recipients assessed 16-20 weeks after their transfer into irradiated secondary mice. The results show that the culture conditions described here support differentiation of ES cells into hematopoietic cells with functional properties of HSC. It should now be possible to unravel the molecular events leading to the formation of HSC.
造血干细胞（HSC）的独特之处在于，它们既能产生新的干细胞（自我更新），又能产生所有类型的血细胞。负责造血干细胞形成的细胞和分子事件仍然未知，主要是因为不存在用于研究它的系统。通过与基质细胞系RP010以及白细胞介素（IL）-3、IL-6和F（来自FLS4.1胎儿肝脏基质细胞系培养物的无细胞上清液）共同培养，诱导胚胎干细胞（ES）分化。对培养物中产生的单核细胞进行细胞流式分析，结果与PgP-1+ Lin-早期造血细胞（B-220- Mac-1- JORO 75- TER 119-）的存在一致，同时存在较少的B-220+ IgM- B细胞祖细胞和JORO 75+ T淋巴细胞祖细胞。诱导ES细胞产生的经细胞分选纯化的PgP-1+ Lin-细胞能够重建受辐照小鼠的淋巴、髓系和红系谱系。ES来源的PgP-1+ Lin-细胞必须具有广泛的自我更新潜力，因为它们能够在二次小鼠受体中产生造血重建。事实上，用诱导ES细胞产生的经PgP-1+ Lin-细胞分选纯化的细胞重建（15 - 18周前）的受辐照小鼠的骨髓细胞，在转移到受辐照的二次小鼠中16 - 20周后，重建了二次小鼠受体的淋巴、髓系和红系谱系。结果表明，本文所述的培养条件支持ES细胞分化为具有造血干细胞功能特性的造血细胞。现在应该有可能揭示导致造血干细胞形成的分子事件。
