The tumor suppressor Fat1 is dispensable for normal murine hematopoiesis

Loss and overexpression of FAT1 occurs among different cancers, with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence po...

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Bibliographic Details
Published in:Journal of leukocyte biology 2024-10, Vol.116 (4), p.909-914
Main Authors: Zhang, Qing, Li, Meng Ke, Hu, Xin Yuan, Wu, Yu Xin, Wang, Ying Ying, Zhao, Pan Pan, Cheng, Lin Na, Yu, Rong Hua, Zhang, Xu Dong, Chen, Song, Zhu, Zun Min, de Bock, Charles E, Thorne, Rick F
Format: Article
Language:English
Subjects:
Animals
Bone Marrow Transplantation
Cadherins
Hematopoiesis
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
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Summary:Loss and overexpression of FAT1 occurs among different cancers, with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets (i.e. sustained following transformation), predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout mice in which Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multipanel flow cytometry revealed no ostensible differences between Fat1 conditional knockout mice and normal littermates. Further functional comparisons involving colony-forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.
ISSN:1938-3673
1938-3673
DOI:10.1093/jleuko/qiae128