Palacios R, Imhof B A
The Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
EMBO J. 1996 Dec 16;15(24):6869-76.
During mouse development, the first lymphohematopoietic precursor cells and myeloid or erythroid cell lineage-determined cells can be detected in the yolk sac at days 8-8.5 of gestation. The characteristics of the cells that give rise to these yolk sac primitive lymphohematopoietic cells and the molecular events controlling this process remain poorly defined. We show here that cell suspensions from day 7 early-mid-primitive streak stage embryo proper generated early immature PgP-1+ Joro 177+ Lin- hematopoietic cells and some Mac-1+ myeloid and TER 119+ erythroid cells after co-culture with the yolk sac-derived stromal cell line YS6 without addition of exogenous cytokines. Purified Lin- hematopoietic cells generated in these cultures did not express genes known to be transcribed at early stages of lymphoid, myeloid or erythroid cell differentiation and were able to give rise to T and B lymphocytes, myeloid cells and erythroid cells after appropriate further induction in vitro. Several cell lines were established in culture with a mixture of four cytokines from the PgP-1+ Joro 177+ Lin- cell population. The cell lines shared phenotypic and genotypic characteristics with the PgP-1+ Joro 177+ Lin- cell population generated in culture from day 7 embryo proper and they were able to reconstitute the lymphohematopoietic system of irradiated mice. Taken together these results support a model of lymphohematopoiesis in which cells from day 7 early-mid-primitive streak mouse embryo proper migrate and colonize the visceral yolk sac. There they generate primitive lymphohematopoietic precursor cells and the first erythroid and myeloid hematopoietic cells under the influence of yolk sac stromal cells like the YS6 cells described here.
在小鼠发育过程中，妊娠第8至8.5天可在卵黄囊中检测到首批淋巴造血前体细胞以及髓系或红系细胞谱系确定细胞。产生这些卵黄囊原始淋巴造血细胞的细胞特征以及控制这一过程的分子事件仍不清楚。我们在此表明，来自妊娠第7天早期至中期原条期胚胎本体的细胞悬液，在与卵黄囊来源的基质细胞系YS6共培养且不添加外源性细胞因子的情况下，产生了早期未成熟的PgP-1⁺ Joro 177⁺ Lin⁻造血细胞以及一些Mac-1⁺髓系细胞和TER 119⁺红系细胞。在这些培养物中产生的纯化Lin⁻造血细胞不表达已知在淋巴系、髓系或红系细胞分化早期转录的基因，并且在体外经过适当的进一步诱导后能够产生T和B淋巴细胞、髓系细胞和红系细胞。用来自PgP-1⁺ Joro 177⁺ Lin⁻细胞群体的四种细胞因子混合物在培养中建立了几个细胞系。这些细胞系与从妊娠第7天胚胎本体培养产生的PgP-1⁺ Joro 177⁺ Lin⁻细胞群体具有共同的表型和基因型特征，并且能够重建受辐照小鼠的淋巴造血系统。综合这些结果支持了一种淋巴造血模型，即来自妊娠第7天早期至中期原条期小鼠胚胎本体的细胞迁移并定殖于内脏卵黄囊。在那里，它们在卵黄囊基质细胞（如本文所述的YS6细胞）的影响下产生原始淋巴造血前体细胞以及首批红系和髓系造血细胞。
