动物造模,造血干细胞 z-bo 2020-09-26 346

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

　　This discovery shows 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 from more mature or differentiated cells.

　　HSC is the basic raw material of HSCT and has nothing to do with the 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 the lead author, Dr. Jonaiddell, screened partial gene expression of 40 genes from mouse blood and blood precursor cells. Through this screening, they determined that only HSC expresses 36 transcription factors. Rossi said: "The production of blood cells is without exception one-way: from stem cells to progenitor cells to mature effector cells." "We want to reverse this process and use HSC-specific transcription factors from differentiated blood cells. Get HSC."

　　In a series of mouse transplant experiments, there are 36 factors in Rossiteam and we found 6 factors. That is, Hlf, Runx1t1, Pbx1, Lmo2, Zfp37 and Prdm5, and the other two factors mycn and Meis1 are sufficient to reprogram two types of blood precursors (pro/preB cells and common bone marrow precursors). Unit) will be 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 showed that it has the ability to produce all blood cell components of mice and differentiate into all blood lines.