动物实验,造血干细胞 z-bio 2021-09-28 664

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

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

　　HSC is the basic raw material for hematopoietic stem cell transplantation, 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 research, Rossi and his colleagues protected 40 different types of genes in mouse blood and blood progenitor cells from partial gene expression, including lead author Dr. Jonaider. Through screening, they determined that 36 transcription factors are only expressed by HSC.

　　"From stem cells to progenitor cells to mature effector cells, the production of blood cells is one-way," Rossi said. "We want to reverse this process and use HSC-specific transcription factors derived from differentiated blood cells to obtain HSC."

　　In a series of mouse transplant experiments, Rossi's team collaborated on 36 factors. Six of them, Hlf, Runx1t1, Pbx1, Lmo2, Zfp37, Prdm5 and the other two factors mycn and Meis1, regenerate two types of blood progenitor cells (pro/preB cells and ordinary bone marrow progenitor cells). Enough for programming, but not found in those screenings. Cell) becomes iHSC.

　　Rossi’s team reprogrammed the source cell in the presence of doxycycline, exposing the cell to a virus containing all eight factor genes and a molecular switch that turns on the factor genes. Cells were transplanted into recipient mice, and doxycycline was given to activate these genes.

　　Result iHSC can produce all blood cell components of mice, indicating that mice have acquired the ability to differentiate into all lineages.