The anti-apoptotic gene Anamorsin is essential for both autonomous and extrinsic regulation of murine fetal liver hematopoiesis.
Anamorsin (AM) is an antiapoptotic molecule that confers factor-independent survival on hematopoietic cells. AM-deficient (AM(-/-)) mice are embryonic lethal because of a defect in definitive hematopoiesis; however, the significance of AM in embryonic hematopoiesis remains unknown. This study characterized the hematopoietic defects in AM(-/-) fetal livers. The AM(-/-) fetal liver displayed significantly reduced numbers of c-Kit(+)Sca-1(+)Lin(-) (KSL) cells. An in vitro colony-forming unit assay showed that fetal liver cells isolated from AM(-/-) embryos gave rise to fewer colonies in all cell types. The reconstitution activity in AM(-/-) hematopoietic stem cells (HSCs) was markedly reduced in all lineages. Furthermore, the limiting dilution assay revealed that the number of fetal liver HSCs was reduced because of AM deficiency. Retrovirus-mediated AM expression rescued the defective hematopoietic colony-forming activities of AM(-/-) KSL cells. We also investigated the effects of AM deficiency on fetal liver stromal cells, which support hematopoiesis. Interestingly, primary stromal cell cultures from wild type fetal liver supported the growth of AM(-/-) KSL cells, but stromal cultures from AM(-/-) fetal liver provided little support of wild type KSL cell growth. These results demonstrated that AM was essential for both autonomous and extrinsic regulation of fetal liver hematopoiesis. This study provided new insight into the molecular regulation of hematopoiesis.
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Akira
A
Tanimura
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address: hiro@bldon.med.osaka-u.ac.jp.
Hirohiko
H
Shibayama
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Yuri
Y
Hamanaka
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Natsuko
N
Fujita
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Tomohiko
T
Ishibashi
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Takao
T
Sudo
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Takafumi
T
Yokota
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Sachiko
S
Ezoe
Division of Hematology, Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan.
Hirokazu
H
Tanaka
Division of Hematology, Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan.
Itaru
I
Matsumura
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Kenji
K
Oritani
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
Yuzuru
Y
Kanakura
D000818:Animals; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D006411:Hematopoiesis, Extramedullary / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
C557202:Ciapin1 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins