Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoietin (Epo) is essential for the later stages of erythropoiesis, acting to promote cell survival and proliferation, but its role in differentiation remains to be defined. The UT-7 cell line exhibits both erythroid and megakaryocytic characteristics and can be induced to differentiate along the erythroid pathway by Epo or the megakaryocytic pathway by phorbol myristic acetate. We have compared the effects of Epo and the chemical inducers, delta-aminolaevulinic acid (delta-ALA) and haemin on the differentiation capacity of UT-7 cells. Epo alone promoted relatively early events in erythroid maturation, without significant changes in haemoglobin production or morphology. GATA-2 and c-myb were down-regulated by Epo, and GATA-2 was further down-modulated by the inducers. Conversely, SCL expression was up-regulated by Epo and further increased by haemin and delta-ALA. Epo caused an increase in the proportion of cells expressing cell surface glycophorin A (GPA) and up-regulated beta- and gamma-globin by several fold. Both haemin and delta-ALA caused a de novo increase in alpha-globin expression as well as enhancing Epo-induced beta-globin expression, leading to a marked increase in haemoglobin production. These results suggest that haemoglobin production in UT-7 cells is limited by a deficiency of erythroid-specific aminolaevulinic acid synthase (ALAS-E) activity or globin synthesis as a consequence of their immaturity as a multipotential cell line.
 ...
PMID:Erythroid gene expression is differentially regulated by erythropoietin, haemin and delta-aminolaevulinic acid in UT-7 cells. 1019 46

GATA transcription factors have been shown to play important roles in hematopoiesis. GATA-2 is expressed in stem and progenitor cells, and has been speculated to control the proliferation and maintain the immaturity of these cells. To examine whether the function of GATA-2 is changeable according to the differentiation stage, we established GATA-2 overexpressing subclones of K562, which is a leukemic cell line committed to the erythroid lineage. Via an increase in the GATA-2 expression level, the expression levels of erythroid-specific genes including alpha-, beta-, and gamma-globin were increased compared to control cells, while the expression level of GATA-1 was unchanged. Expression of the transferrin receptor was also increased in GATA-2 overexpressing K562 cells when examined by flow cytometry. In addition, the heme content of GATA-2 overexpressing K562 cells was more than 2 times higher than control cells. Chromatin immunoprecipitation analysis showed that GATA-2 protein binding to the GATA element in alpha-globin LCR was increased in GATA-2 overexpressing K562 cells. These findings suggest that GATA-2 could induce erythroid-specific genes without competition with GATA-1 when expressed in erythroid-committed cells, and thus further suggest that temporal and spatial regulation may be important for displaying specific functions of GATA-2.
 ...
PMID:Induction of erythroid-specific genes by overexpression of GATA-2 in K562 cells. 1686