Chemical control of cell differentiation and its commitment of blood cells

人髓系白血病K562细胞被诱导向成熟细胞双向分化，即血红素诱导红细胞分化，而12-O-tetradecanoylphorbol 13-acetate （TPA）诱导单核细胞分化。TPA是一种有效的血红素加氧酶（HO）诱导剂，它将血红素分解为胆绿素。一种HO抑制剂，锡原卟啉（SnPP），抑制tpa诱导的K562细胞向单核细胞的分化。我们发现TPA抑制血红素诱导的K562细胞红系分化，而类维生素a则增强这种分化。此外，HO抑制剂锡原卟啉（SnPP）可抑制tpa诱导的K562细胞向单核细胞的分化。我们还发现，K562细胞与SnPP和TPA共处理可诱导K562细胞的红系分化，但单独使用SnPP或TPA均不能诱导红系分化，提示HO在分化的方向开关中起作用。

Human myeloid leukemia K562 cells be induced to differentiate to mature cells bidirectionary, i.e., hemin induces erythroid differentiation, while 12-O-tetradecanoylphorbol 13-acetate (TPA) induces differentiation to monocytes. TPA is a potent inducer of heme oxygenase (HO), which catabolizes heme to biliverdin. An HO inhibitor, tin protoporphyrin (SnPP), suppresses TPA-induced K562 cell differentiation to monocytes. We show that TPA suppresses hemin-induced erythroid differentiation of K562 cells, while retinoids augment it. Futher, an HO inhibitor, tin protoporphyrin (SnPP), suppresses TPA-induced K562 cell differentiation to monocytes. It was also found that co-treatment of K562 cells with SnPP and TPA induces erythroid differentiation of K562 cells, though SnPP alone or TPA alone does not induce erythroid differentiation, suggesting a role of HO in the directional switch of differentiation.