Abstract
Objective: To search a novel function of erythroid progenitor cells circulating as the major nucleated cell population in umbilical cord blood (CB) cells. Materials and Methods: Human CB-derived CD36+ erythroid progenitors were subjected to cDNA microarray. Gene expression and biological property of CB-erythroid progenitors and adult peripheral blood (PB)-erythroid progenitors were compared by using real-time polymerase chain reaction (PCR) and serum-free culture system with erythropoietin (EPO). Results: The microarray revealed 124-fold higher levels of insulin-like growth factor-II (IGF-II) gene expression in CB-CD36+ erythroid progenitors than in stimulated lymphocytes of adult PB. Real-time PCR verified that IGF-II mRNA levels were highest in CB-CD36+ erythroid progenitors compared to other CB- or adult PB-fractionated cells. When CB-CD36+ erythroid progenitors were cultured with EPO in serum-free medium, anti-IGF-II-antibody (Ab) reduced the number of erythroid colonies. When CB- and adult PB-derived erythroid colony-forming cells (ECFCs) were cultured with interleukin-3, stem cell factor, and EPO, mRNA levels per cells of IGF-II peaked on day 12, but those of type 1 and type 2 receptors did not increase with ECFCs maturation. The maturation rate by IGF-II was higher in CB-ECFCs than in adult PB-ECFCs. The majority of CB-ECFCs expressed IGF-II protein. Anti-IGF-II-Ab, but not anti-IGF-I-Ab, reduced the number of CB-ECFCs in liquid culture with EPO. Anti-IGF-II-Ab accelerated apoptosis of ECFCs, assessed by dimethylthiazole tetrazolium bromide, bromodeoxyuridine, and flow cytometric analyses. ECFCs failed to attain full maturity in the presence of anti-IGF-II-Ab. Conclusions: These results suggest that IGF-II is produced by erythroid progenitors themselves, and has a crucial role in fetal erythropoiesis by modulating apoptosis and maturation in an autocrine fashion.
| Original language | English |
|---|---|
| Pages (from-to) | 401-411 |
| Number of pages | 11 |
| Journal | Experimental Hematology |
| Volume | 36 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2008 |
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All Science Journal Classification (ASJC) codes
- Cancer Research
- Cell Biology
- Genetics
- Hematology
- Oncology
- Transplantation
Cite this
Insulin-like growth factor-II : a novel autocrine growth factor modulating the apoptosis and maturation of umbilical cord blood erythroid progenitors. / Nagatomo, Taro; Muta, Koichiro; Ohga, Shoichi; Ochiai, Masayuki; Ohshima, Koichi; Hara, Toshiro.
In: Experimental Hematology, Vol. 36, No. 4, 01.04.2008, p. 401-411.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Insulin-like growth factor-II
T2 - a novel autocrine growth factor modulating the apoptosis and maturation of umbilical cord blood erythroid progenitors
AU - Nagatomo, Taro
AU - Muta, Koichiro
AU - Ohga, Shoichi
AU - Ochiai, Masayuki
AU - Ohshima, Koichi
AU - Hara, Toshiro
PY - 2008/4/1
Y1 - 2008/4/1
N2 - Objective: To search a novel function of erythroid progenitor cells circulating as the major nucleated cell population in umbilical cord blood (CB) cells. Materials and Methods: Human CB-derived CD36+ erythroid progenitors were subjected to cDNA microarray. Gene expression and biological property of CB-erythroid progenitors and adult peripheral blood (PB)-erythroid progenitors were compared by using real-time polymerase chain reaction (PCR) and serum-free culture system with erythropoietin (EPO). Results: The microarray revealed 124-fold higher levels of insulin-like growth factor-II (IGF-II) gene expression in CB-CD36+ erythroid progenitors than in stimulated lymphocytes of adult PB. Real-time PCR verified that IGF-II mRNA levels were highest in CB-CD36+ erythroid progenitors compared to other CB- or adult PB-fractionated cells. When CB-CD36+ erythroid progenitors were cultured with EPO in serum-free medium, anti-IGF-II-antibody (Ab) reduced the number of erythroid colonies. When CB- and adult PB-derived erythroid colony-forming cells (ECFCs) were cultured with interleukin-3, stem cell factor, and EPO, mRNA levels per cells of IGF-II peaked on day 12, but those of type 1 and type 2 receptors did not increase with ECFCs maturation. The maturation rate by IGF-II was higher in CB-ECFCs than in adult PB-ECFCs. The majority of CB-ECFCs expressed IGF-II protein. Anti-IGF-II-Ab, but not anti-IGF-I-Ab, reduced the number of CB-ECFCs in liquid culture with EPO. Anti-IGF-II-Ab accelerated apoptosis of ECFCs, assessed by dimethylthiazole tetrazolium bromide, bromodeoxyuridine, and flow cytometric analyses. ECFCs failed to attain full maturity in the presence of anti-IGF-II-Ab. Conclusions: These results suggest that IGF-II is produced by erythroid progenitors themselves, and has a crucial role in fetal erythropoiesis by modulating apoptosis and maturation in an autocrine fashion.
AB - Objective: To search a novel function of erythroid progenitor cells circulating as the major nucleated cell population in umbilical cord blood (CB) cells. Materials and Methods: Human CB-derived CD36+ erythroid progenitors were subjected to cDNA microarray. Gene expression and biological property of CB-erythroid progenitors and adult peripheral blood (PB)-erythroid progenitors were compared by using real-time polymerase chain reaction (PCR) and serum-free culture system with erythropoietin (EPO). Results: The microarray revealed 124-fold higher levels of insulin-like growth factor-II (IGF-II) gene expression in CB-CD36+ erythroid progenitors than in stimulated lymphocytes of adult PB. Real-time PCR verified that IGF-II mRNA levels were highest in CB-CD36+ erythroid progenitors compared to other CB- or adult PB-fractionated cells. When CB-CD36+ erythroid progenitors were cultured with EPO in serum-free medium, anti-IGF-II-antibody (Ab) reduced the number of erythroid colonies. When CB- and adult PB-derived erythroid colony-forming cells (ECFCs) were cultured with interleukin-3, stem cell factor, and EPO, mRNA levels per cells of IGF-II peaked on day 12, but those of type 1 and type 2 receptors did not increase with ECFCs maturation. The maturation rate by IGF-II was higher in CB-ECFCs than in adult PB-ECFCs. The majority of CB-ECFCs expressed IGF-II protein. Anti-IGF-II-Ab, but not anti-IGF-I-Ab, reduced the number of CB-ECFCs in liquid culture with EPO. Anti-IGF-II-Ab accelerated apoptosis of ECFCs, assessed by dimethylthiazole tetrazolium bromide, bromodeoxyuridine, and flow cytometric analyses. ECFCs failed to attain full maturity in the presence of anti-IGF-II-Ab. Conclusions: These results suggest that IGF-II is produced by erythroid progenitors themselves, and has a crucial role in fetal erythropoiesis by modulating apoptosis and maturation in an autocrine fashion.
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U2 - 10.1016/j.exphem.2007.12.009
DO - 10.1016/j.exphem.2007.12.009
M3 - Article
VL - 36
SP - 401
EP - 411
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 4
ER -