Hematopoietic stem cells (HSCs) are adult stem cells in the blood system. They are a heterogeneous population with the ability of long-term self-renewal and the potential to differentiate into various mature blood cells.It is a kind of adult stem cells with the longest and most in-depth research history, and has important guiding significance for the research of all kinds of stem cells, including tumor stem cells.
The life of mature cells in the blood system is extremely short, so in the life of human beings, hematopoietic stem cells need to timely supplement each mature cell component of the blood system according to the physiological needs of the body.At the same time, under stress conditions such as injury and inflammation, hematopoietic stem cells also play a role in regulating and maintaining the physiological balance of various cell components of the blood system in the body.In 1961, Till JE and McCulloch EA confirmed the existence of hematopoietic stem cells for the first time with the method of spleen nodules in mice.After the 1980s, Weissman and other laboratories successively separated highly purified hematopoietic stem progenitor cells at different stages through cell surface markers.In the study of mouse hematopoietic stem cells, the separation of hematopoietic stem cells is achieved by cell surface labeling Lineage Sca-1c-kit or cell metabolism characteristics (side group cells) with flow cytometry.In the 1990s, CD34, a cell surface marker, was introduced to distinguish between long-term and short-term hematopoietic stem cells in mice.In the 21st century, based on SLAM family molecules (CD41, CD48 and CD150), further enrich hematopoietic stem cells. The expression of SLAM molecules in hematopoietic stem cells is relatively stable and can be widely used in various strains of experimental mice.The research on human HSC surface labeling has also developed synchronously. At present, the widely used human hematopoietic stem cell surface labeling is LineageCD34CD38.
Relationship with tumor
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grossleukemiaIn particular, the occurrence of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) is directly or indirectly related to abnormal hematopoietic stem cells.CML is a common type of leukemia with the most classic chromosome translocation leading to malignant transformation of hematopoietic stem cells, and most other acute myeloid leukemia come from malignant transformation of progenitor cells directly.Hematopoietic stem cells are the first to obtain major pathogenic mutations such as chromosome translocation, but this does not affect their ability to differentiate into normal functioning mature cells. When the hematopoietic stem cells with chromosome translocation or the cells downstream of their differentiation get a second hit, leukemia will be triggered.
Hematopoietic stem cells also play a certain role in the regulation of solid tumor microenvironment. For example, prostate tumor cells will simulate the molecular signals of hematopoietic stem cells, enter the hematopoietic microenvironment, and cause changes in the expression profile of hematopoietic stem cells to force hematopoietic stem cells to leave, or they can leave the hematopoietic microenvironment by expressing molecules related to the migration of hematopoietic cells, ultimately leading to tumor metastasis.
In clinical treatment, hematopoietic stem cell transplantation is widely used in the treatment of hematological diseases and autoimmune diseases. In the treatment of other solid tumors, such as lymphoma, germ cell tumor, breast cancer, small cell lung cancer, it is mainly used in patients who have failed conventional treatment or relapse and are refractory and have adverse prognostic factors.
scientific research
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In September 2022,Australian researchers conducted two studies, which not only revealed how hematopoietic stem cell precursors were produced in animals and humans, but also revealed how they were artificially induced.[1]
