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During the War Years, the allusion of Mengzi, a generation of thinkers, was a household name, and this story shows the importance of environmental factors.
in organisms, the micro-environment is also an indispensable factor in the multi-step, multi-stage development of hematopoietic stem cells.
Vertebrate hematopoietic stem cells are produced in the aorta-gland-middle kidney region and then migrated to fetal liver (mice and humans) or tail hematopoietic tissue (zebrafish) for amplification, which in turn migrates to thymus-to-go differentiation, and finally to bone marrow (mice and humans) or kidney myelin (zebrafish) to sustain lifelong hematopoietic blood production.
it can be seen that at different stages of hematopoietic stem cell development, there are specific micro-environments to regulate it.
, how to regulate the expansion of hematopoietic stem cells has become one of the hot issues in this field.
In view of the limitations of intrateral development of mouse embryos and early death of some mutants, the blood and cardiovascular development research group led by Liu Feng, a researcher at the Institute of Zoology of the Chinese Academy of Sciences, focused on the role and mechanism of vascular endoder cells in endometriosis tissue on the amplification of hematopoietic stem cells in zebrafish.
1: Vascular endotymus cells regulate the presence and proliferation of hematopoietic stem cells by secreting important chemic factors.
In normal individuals, zebrafish tail hematopoietic tissue not only provides a physical living environment for hematopoietic stem cells, but also endopilative cells can attract hematopoietic stem cells to reside in them by secreting a chemizing factor to promote the proliferation of stem cells.
In individuals with klf6a defects, structural disorders of the tail blood vessels and a sharp decrease in the curvatization factor cl25b of the endodermic source of the blood vessels destroyed the microencourse in which hematopoietic stem cells reside, resulting in a decrease in the presence and proliferation of hematopoietic stem cells in the tail hematopoietic tissue. The
team took full advantage of zebrafish's inositive development and early embryo transparency, and observed in real time through a laser confocal microscope that hematopoietic stem cells in the tail hematopoietic tissue were adjacent to the endotrine cells of the blood vessels, and that their migration and amplification had a tail vein-specific orientation.
suggests that endogenic endocytes are an important factor in the microencellular environment of hematopoietic stem cells.
analysis of genome-wide expression spectrometry in vascular endotythroid cells, hematopoietic stem cells, and other cell groups in the tail hematopoietic tissue, a transcription factor specific to endotythroids, Klf6a, was found.
knocking down or knocking out klf6a can lead to defects in the microencular endoensis of blood vessels in the hematopoietic tissue of zebrafish tails, thus impeding the presence and amplification of hematopoietic stem cells.
in-depth molecular mechanism exploration found that Klf6 can directly regulate the expression of the trending factor ccl25b, through the Ccl25b/Ccr7 trending signal to affect hematopoietic stem cell amplification.
addition, the results of in-body culture experiments on lethlete liver LSK cells (Lin-Sca-1-c-Kit)) in mice showed that the molecular mechanism was also conservative in higher mammalian fetal liver hematomatosis.
The above work reveals the new molecular mechanism of hematopoietic microencity on hematopoietic stem cell regulation, and finds that Klf6a-Ccl25b/Ccr7 signal axis mediats the amplification of hematopoietic stem cells, and will also provide theoretical guidance for in-body amplification and transplantation of hematopoietic stem cells.
research paper The vascular niche regulates hematopoietic stem and progenitor cell lodgement and expansion via klf6a-ccl25b was published online August 10 in Development Cell.
Ph.D. student Xue Wei is the first author, Liu Feng is the communication author, the subject has been the National Science Foundation for Distinguished Young People, the National Natural Science Foundation key projects, the National Key Basic Research and Development Program and the Chinese Academy of Sciences stem cell and regenerative medicine strategic pilot science and technology special funding.
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