The secreted lymphangiogenic factor CCBE1 is essential for fetal liver erythropoiesis.

Zhiying Zou, David R. Enis, Hung Bui, Eugene Khandros, Vinayak Kumar, Z. Jakus, Christopher Thom, Yiqing Yang, Veerpal Dhillon, Mei Chen, Minmin Lu, Mitchell J. Weiss, Mark L. Kahn

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The secreted protein CCBE1 is required for lymphatic vessel growth in fish and mice, and mutations in the CCBE1 gene cause Hennekam syndrome, a primary human lymphedema. Here we show that loss of CCBE1 also confers severe anemia in midgestation mouse embryos due to defective definitive erythropoiesis. Fetal liver erythroid precursors of Ccbe1 null mice exhibit reduced proliferation and increased apoptosis. Colony-forming assays and hematopoietic reconstitution studies suggest that CCBE1 promotes fetal liver erythropoiesis cell nonautonomously. Consistent with these findings, Ccbe1(lacZ) reporter expression is not detected in hematopoietic cells and conditional deletion of Ccbe1 in hematopoietic cells does not confer anemia. The expression of the erythropoietic factors erythropoietin and stem cell factor is preserved in CCBE1 null embryos, but erythroblastic island (EBI) formation is reduced due to abnormal macrophage function. In contrast to the profound effects on fetal liver erythropoiesis, postnatal deletion of Ccbe1 does not confer anemia, even under conditions of erythropoietic stress, and EBI formation is normal in the bone marrow of adult CCBE1 knockout mice. Our findings reveal that CCBE1 plays an essential role in regulating the fetal liver erythropoietic environment and suggest that EBI formation is regulated differently in the fetal liver and bone marrow.

Original languageEnglish
Pages (from-to)3228-3236
Number of pages9
JournalBlood
Volume121
Issue number16
DOIs
Publication statusPublished - Apr 18 2013

Fingerprint

Erythropoiesis
Liver
Anemia
Bone
Embryonic Structures
Bone Marrow
Stem Cell Factor
Lymphatic Vessels
Lymphedema
Macrophages
Erythropoietin
Knockout Mice
Fish
Assays
Fishes
Genes
Apoptosis
Mutation
Growth
Proteins

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Zou, Z., Enis, D. R., Bui, H., Khandros, E., Kumar, V., Jakus, Z., ... Kahn, M. L. (2013). The secreted lymphangiogenic factor CCBE1 is essential for fetal liver erythropoiesis. Blood, 121(16), 3228-3236. https://doi.org/10.1182/blood-2012-10-462689

The secreted lymphangiogenic factor CCBE1 is essential for fetal liver erythropoiesis. / Zou, Zhiying; Enis, David R.; Bui, Hung; Khandros, Eugene; Kumar, Vinayak; Jakus, Z.; Thom, Christopher; Yang, Yiqing; Dhillon, Veerpal; Chen, Mei; Lu, Minmin; Weiss, Mitchell J.; Kahn, Mark L.

In: Blood, Vol. 121, No. 16, 18.04.2013, p. 3228-3236.

Research output: Contribution to journalArticle

Zou, Z, Enis, DR, Bui, H, Khandros, E, Kumar, V, Jakus, Z, Thom, C, Yang, Y, Dhillon, V, Chen, M, Lu, M, Weiss, MJ & Kahn, ML 2013, 'The secreted lymphangiogenic factor CCBE1 is essential for fetal liver erythropoiesis.', Blood, vol. 121, no. 16, pp. 3228-3236. https://doi.org/10.1182/blood-2012-10-462689
Zou, Zhiying ; Enis, David R. ; Bui, Hung ; Khandros, Eugene ; Kumar, Vinayak ; Jakus, Z. ; Thom, Christopher ; Yang, Yiqing ; Dhillon, Veerpal ; Chen, Mei ; Lu, Minmin ; Weiss, Mitchell J. ; Kahn, Mark L. / The secreted lymphangiogenic factor CCBE1 is essential for fetal liver erythropoiesis. In: Blood. 2013 ; Vol. 121, No. 16. pp. 3228-3236.
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