Kaufman D S, Hanson E T, Lewis R L, Auerbach R, Thomson J A
Section of Hematology, Department of Internal Medicine, University of Wisconsin Hospital and Clinics, 600 Highland Avenue, Madison, WI 53792, USA.
Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10716-21. doi: 10.1073/pnas.191362598. Epub 2001 Sep 4.
Human embryonic stem (ES) cells are undifferentiated, pluripotent cells that can be maintained indefinitely in culture. Here we demonstrate that human ES cells differentiate to hematopoietic precursor cells when cocultured with the murine bone marrow cell line S17 or the yolk sac endothelial cell line C166. This hematopoietic differentiation requires fetal bovine serum, but no other exogenous cytokines. ES cell-derived hematopoietic precursor cells express the cell surface antigen CD34 and the hematopoietic transcription factors TAL-1, LMO-2, and GATA-2. When cultured on semisolid media with hematopoietic growth factors, these hematopoietic precursor cells form characteristic myeloid, erythroid, and megakaryocyte colonies. Selection for CD34(+) cells derived from human ES cells enriches for hematopoietic colony-forming cells, similar to CD34 selection of primary hematopoietic tissue (bone marrow, umbilical cord blood). More terminally differentiated hematopoietic cells derived from human ES cells under these conditions also express normal surface antigens: glycophorin A on erythroid cells, CD15 on myeloid cells, and CD41 on megakaryocytes. The in vitro differentiation of human ES cells provides an opportunity to better understand human hematopoiesis and could lead to a novel source of cells for transfusion and transplantation therapies.
人胚胎干细胞（ES细胞）是未分化的多能细胞，可在培养中无限期维持。我们在此证明，当与人骨髓细胞系S17或卵黄囊内皮细胞系C166共培养时，人ES细胞可分化为造血前体细胞。这种造血分化需要胎牛血清，但不需要其他外源性细胞因子。ES细胞来源的造血前体细胞表达细胞表面抗原CD34以及造血转录因子TAL-1、LMO-2和GATA-2。当在含有造血生长因子的半固体培养基上培养时，这些造血前体细胞形成特征性的髓系、红系和巨核细胞集落。从人ES细胞衍生的CD34(+)细胞的选择富集了造血集落形成细胞，类似于对原发性造血组织（骨髓、脐带血）的CD34选择。在这些条件下从人ES细胞衍生的更多终末分化造血细胞也表达正常表面抗原：红系细胞上的血型糖蛋白A、髓系细胞上的CD15和巨核细胞上的CD41。人ES细胞的体外分化为更好地理解人类造血提供了机会，并可能导致一种用于输血和移植治疗的新型细胞来源。
