The Development and Disease Research Group of the Key Laboratory of Stem Cell Biology of the Chinese Academy of Sciences recently published the latest research results Dominant-Negative C / ebpÎ± and Polycomb Group Protein Bmi1 Extends Short-Lived Hematopoietic Stem / Progenitor Cells Lifespan and Induces Lethal Dyserythropoiesis.
This study used zebrafish as a model organism to study the role of key regulatory factors C / ebpÎ± and Bmi1 in the development of hematopoietic development and leukemia in early hematopoietic stem / progenitor cell survival and maintenance of self-renewal capacity, and established hematopoietic An abnormally developed zebrafish disease model. This achievement provides a new basis for understanding the molecular regulation pathway of hematopoietic stem cell self-renewal and further exploring the mechanism of hematopoietic system development and disease occurrence.
Under the guidance of researchers, Zhou Ting, a PhD student in the research group, used the lmo2 promoter specific to early hematopoietic tissue and the Cre-loxP system to specifically express the leukemia key factor C / ebpÎ± in zebrafish early hematopoietic stem / progenitor cells Dominant negative protein and Bmi1 protein. It was found that the dominant negative C / ebpÎ± protein (Dominant-Negative C / ebpÎ±) can extend the cell life span of this group of short-lived stem cells with limited self-renewal capacity to the stage of embryonic hematopoiesis, and In turn, it induces erythropoietic dysplasia.
Further studies have confirmed that the C / ebpÎ± protein can specifically bind the C / EBP binding sequence of the Bmi1 gene promoter region to increase the specificity of Bmi1 expression in the C / ebpÎ± dominant negative transgenic fish line; Sexual overexpression of Bmi1 can obtain a phenotype that is very similar to the C / ebpÎ± dominant negative transgenic fish line, otherwise the abnormal phenotype can basically disappear. These results suggest that the epigenetic regulatory factor Bmi1 may be directly downstream of the C / ebpÎ± protein. The dominant negative C / ebpÎ± protein affects the survival and self-renewal ability of early hematopoietic stem / progenitor cells by upregulating Bmi1.
This work was supported by funds from the Ministry of Science and Technology, the National Natural Science Foundation of China, the Shanghai Municipal Science and Technology Commission, the Chinese Academy of Sciences, and the E-Institute of Shanghai Municipal Education Commission.
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