Phosphatidylserine receptor is required for the engulfment of dead apoptotic cells and for normal embryonic development in zebrafish

Hematopoiesis, the process of blood formation, is controlled by a complex developmental program that involves intrinsic and extrinsic regulators. Blood formation is critical to normal embryonic development and during embryogenesis distinct waves of hematopoiesis have been defined that represent the emergence of hematopoietic stem or progenitor cells. The Class I family of homeobox (HOX) genes are also critical for normal embryonic development, whereby mutations are associated with malformations and deformity. Recently, members of the HOXA cluster (comprising 11 genes and non-coding RNA elements) have been associated with the emergence and maintenance of long-term repopulating HSCs. Previous studies identified a gradient of HOXA expression from high in HSCs to low in circulating peripheral cells, indicating their importance in maintaining blood cell numbers and differentiation state. Indeed, dysregulation of HOXA genes either directly or by genetic lesions of upstream regulators correlates with a malignant phenotype. This review discusses the role of the HOXA cluster in both HSC emergence and blood cancer formation highlighting the need for further research to identify specific roles of these master regulators in normal and malignant hematopoiesis.

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Nicotinamide Phosphoribosyl Transferase Is Required For Both Normal Embryonic Development And Adult Survival In Mice

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a3539 ◽

2011 ◽

Author(s):

Li Q Zhang ◽

Daniel P. Heruth ◽

Marianne Nsumu ◽

Inna Sokolovsky ◽

Margaret Gibson ◽

...

Keyword(s):

Embryonic Development ◽

Adult Survival ◽

Phosphoribosyl Transferase ◽

Nicotinamide Phosphoribosyl Transferase ◽

Normal Embryonic Development

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Defective fetal liver erythropoiesis and T lymphopoiesis in mice lacking the phosphatidylserine receptor

Blood ◽

10.1182/blood-2003-09-3245 ◽

2004 ◽

Vol 103 (9) ◽

pp. 3362-3364 ◽

Cited By ~ 78

Author(s):

Yuya Kunisaki ◽

Sadahiko Masuko ◽

Mayuko Noda ◽

Ayumi Inayoshi ◽

Terukazu Sanui ◽

...

Keyword(s):

Inflammatory Responses ◽

Apoptotic Cell ◽

Fetal Liver ◽

Lymphoid Cells ◽

Cell Uptake ◽

Developmental Defect ◽

Apoptotic Cells ◽

Phosphatidylserine Receptor ◽

T Lymphopoiesis

Abstract Clearance of apoptotic cells by macrophages is considered important for prevention of inflammatory responses leading to tissue damage. The phosphatidylserine receptor (PSR), which specifically binds to phosphatidylserine (PS) exposed on the surface of apoptotic cells, mediates uptake of apoptotic cells in vitro, yet the physiologic relevance of PSR remains unknown. This issue was addressed by generating PSR-deficient (PSR-/-) mice. PSR-/- mice exhibited severe anemia and died during the perinatal period. In the PSR-/- fetal livers, erythroid differentiation was blocked at an early erythroblast stage. In addition, PSR-/- embryos exhibited thymus atrophy owing to a developmental defect of T-lymphoid cells. Clearance of apoptotic cells by macrophages was impaired in both liver and thymus of PSR-/- embryos. However, this did not induce up-regulation of inflammatory cytokines. These results indicate that during embryonic development, PSR-mediated apoptotic cell uptake is required for definitive erythropoiesis and T lymphopoiesis, independently of the prevention of inflammatory responses. (Blood. 2004;103:3362-3364)

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