Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, BMC A12, 221 84 Lund, Sweden.
Stem Cell Laboratory, Lund University Stem Cell Center, Lund University, BMC B10, 221 84 Lund, Sweden.
Stem Cell Reports. 2015 Feb 10;4(2):269-81. doi: 10.1016/j.stemcr.2015.01.009.
The functions of retinoic acid (RA), a potent morphogen with crucial roles in embryogenesis including developmental hematopoiesis, have not been thoroughly investigated in the human setting. Using an in vitro model of human hematopoietic development, we evaluated the effects of RA signaling on the development of blood and on generated hematopoietic progenitors. Decreased RA signaling increases the generation of cells with a hematopoietic stem cell (HSC)-like phenotype, capable of differentiation into myeloid and lymphoid lineages, through two separate mechanisms: by increasing the commitment of pluripotent stem cells toward the hematopoietic lineage during the developmental process and by decreasing the differentiation of generated blood progenitors. Our results demonstrate that controlled low-level RA signaling is a requirement in human blood development, and we propose a new interpretation of RA as a regulatory factor, where appropriate control of RA signaling enables increased generation of hematopoietic progenitor cells from pluripotent stem cells in vitro.
维甲酸（RA）是一种具有强大形态发生功能的物质，在胚胎发生中具有至关重要的作用，包括发育中的造血作用。然而，RA 在人类环境中的作用尚未得到彻底研究。我们使用人类造血发育的体外模型，评估了 RA 信号对血液发育和生成的造血祖细胞的影响。减少 RA 信号通过两种独立的机制增加了具有造血干细胞（HSC）样表型的细胞的生成，这些细胞能够分化为髓系和淋巴系：通过在发育过程中增加多能干细胞向造血谱系的定向，以及通过减少生成的血液祖细胞的分化。我们的结果表明，受控的低水平 RA 信号是人类血液发育的必要条件，我们提出了 RA 作为调节因子的新解释，其中 RA 信号的适当控制能够增加体外多能干细胞生成造血祖细胞。
