动物造模,造血干细胞 z-bio 2021-10-21 358

　　Researchers at Boston Children's Hospital have used a mixture of transcription factors composed of eight gene switches to reprogram mature mouse blood cells into hematopoietic stem cells (HSC). The researchers who reprogram the cells call it inducible HSC (iHSC), which has the functional signs of HSC, can regenerate itself like HSC, and can produce all blood cell components like HSC.

　　This discovery indicates an important step towards the main goal of regenerative medicine. The ability to produce HSC is suitable for hematopoietic stem cell transplantation (HSCT) from other cell types, especially more mature and differentiated cells. HSC is the basic raw material of HSCT, regardless of its source (bone marrow, cord blood, peripheral blood). The success of hematopoietic stem cell transplantation in individual patients depends on the number of hematopoietic stem cells available for transplantation. The more cells, the greater the possibility of transplantation. However, hematopoietic stem cells are extremely rare.

　　In their study, Rossi and his colleagues, including lead author Dr. Jonaiddell, protected 40 genes in mouse blood and blood progenitor cells from partial gene expression. Through this screening, they determined that only HSC expresses 36 transcription factors. Rossi said: "The production of blood cells is one-way without exception: from stem cells to progenitor cells to mature effector cells." "We want to reverse this process and use HSC-specific transcription from differentiated blood cells. Factor to obtain HSC."

　　In a series of mouse transplant experiments, Rossiteam hopes to obtain 36 factors. We found 6 of them: Hlf, Runx1t1 and Pbx1. Lmo2, Zfp37, Prdm5, and the other two factors mycn and Meis1 are sufficient to reprogram two blood progenitor cells (pro/preB cells and common bone marrow progenitor cells) into iHSC.

　　The ossi team reprogrammed the source cell by exposing the virus containing all eight factor genes and turning on the molecular switch of the factor genes in the presence of doxycycline. The exposed cells were then transplanted into recipient mice and doxycycline was given to activate these genes.

　　"Results iHSC can produce all blood cell components of mice. This shows that iHSC has the ability to differentiate into all blood lines.