动物实验,造血干细胞 z-bo 2020-08-31 545

　　Researchers at Boston Children's Hospital reprogrammed mice’s mature blood cells into blood-forming hematopoietic stem cells (HSCs), using a mixture of transcription factors composed of eight gene switches. Reprogramming cells researchers call it induced HSCs (iHSCs), which have the functional signature of HSCs, can renew themselves like HSCs, and can produce all blood cell components like HSCs.

　　This discovery marks another important step towards the main goal of regenerative medicine: the ability to produce HSCs is suitable for hematopoietic stem cell transplantation (HSCT) from other cell types, especially more mature or differentiated cells.

　　HSCs are the basic raw materials of HSCTs, regardless of their source (bone marrow, cord blood, peripheral blood). The success of any individual patient's hematopoietic stem cell transplantation depends on the number of hematopoietic stem cells available for transplantation: the more cells, the more likely the transplantation will prevail. However, hematopoietic stem cells are quite rare.

　　In their study, Rossi and his colleagues, including the lead author, Dr. Jonah Riddell, screened 40 different types of genes in mouse blood and blood progenitor cells from partial gene expression. Through this screening, they determined that 36 transcription factors are expressed only by HSCs.

　　"The production of blood cells is in one direction without exception: from stem cells, to progenitor cells, to mature effector cells," Rossi said. "We want to use transcription factors that are unique to HSCs from differentiated blood cells to reverse this process and obtain HSCs."

　　In a series of mouse transplant experiments, the Rossi team found that 6 of the 36 factors are Hlf, Runx1t1, Pbx1, Lmo2, Zfp37 and Prdm5. The other 2 factors were not found in their screening, namely mycn and Meis1. , Is enough to reprogram two kinds of blood progenitor cells (pro/pre B cells and common bone marrow progenitor cells) into iHSCs.

　　Rossi's team reprogrammed the source cells by exposing them to a virus containing all 8 factor genes and a molecular switch that turns on the factor genes and in the presence of doxycycline. They then transplanted the exposed cells into recipient mice and gave them doxycycline to activate these genes.

　　"Results iHSCs can produce all blood cell components in mice, showing that they have acquired the ability to differentiate into all blood lineages.