[Animal Modeling]-Mechanism of Ncor2 Regulating the Development of Zebrafish Hematopoietic Stem Cells

  Hematopoietic stem cells are a group of multipotent hematopoietic progenitor cells necessary to maintain the normal physiological functions of living organisms. They can develop into various mature blood cells, including red blood cells, myeloid cells and lymphocytes. The hematopoietic process of zebrafish is divided into two stages, namely: primary hematopoiesis and secondary hematopoiesis.

  Previous studies have shown that the transcriptional co-repressor Ncor2 plays a role in primary hematopoiesis, but its effect on secondary hematopoiesis, especially on hematopoietic stem cells, is still unclear.

  The blood and cardiovascular development research group led by researcher Feng Liu found that ncor2 is specifically expressed in the secondary hematopoietic region of zebrafish-aorta-gonad-mesokidney (AGM) and hematopoietic stem cells (HSC). Knockdown or knockout of ncor2 will result in a decrease in the number of hematopoietic stem cells and T cells. Further research found that Ncor2 and Hdac3 jointly inhibit the expression of fos gene. The decrease of ncor2 will lead to the increase of fos expression level, the fate of blood vessels is strengthened, and the inner diameter of arteries becomes larger. The increase of fos will promote the expression of vegfd, activate the Notch signaling pathway, and then inhibit the production of hematopoietic stem cells.

  The research results revealed the mechanism of Ncor2 in the development of zebrafish hematopoietic stem cells, enriched our understanding of the development process of hematopoietic stem cells, and provided a theoretical basis for the expansion of hematopoietic stem cells in vitro.

  The above research results were published online in Blood on July 8th, with Wei Yonglong, a doctoral student in the research group, as the first author of the paper; and researcher Liu Feng as the corresponding author. This research work has been supported by the National Key Basic Research and Development Program, the National Natural Science Foundation of China, the Hundred Talents Program of the Chinese Academy of Sciences, and the Strategic Leading Science and Technology Project of the Chinese Academy of Sciences.