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in the bone marrow
Scientists have reported a method for equipping mouse hematopoietic stem cells (HSCs) with a fluorescent marker that can be switched on from the outside.
Using this tool, they were able to observe how HSCs mature into blood cells under normal conditions, and they developed a mathematical model of the dynamics of hematopoiesis.
The research suggests the normal process of hematopoiesis differs from what scientists previously assumed when using data from stem cell transplants.
“[A] problem with almost all research on hematopoiesis in past decades is that it has been restricted to experiments in culture or using transplantation into mice,” said study author Hans-Reimer Rodewald, PhD, of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg.
“We have now developed the first model where we can observe the development of a stem cell into a mature blood cell in a living organism.”
The researchers described this model in Nature.
The team genetically modified mice by introducing a protein into their HSCs that sends out a yellow fluorescent signal. This marker can be turned on by administering a reagent. All daughter cells that arise from a cell containing the marker also send out a light signal.
When they turned on the marker in adult mice, the researchers observed that at least a third of a mouse’s HSCs (approximately 5000 cells) produce differentiated progenitor cells.
“This was the first surprise,” said study author Katrin Busch, also of DKFZ. “Until now, scientists had believed that, in the normal state, very few stem cells—only about 10—are actively involved in blood formation.”
The researchers performed a mathematical analysis of these experimental data to provide additional insight into blood stem cell dynamics. They were surprised to find that, under normal conditions, HSCs do not replenish blood cells.
Instead, blood cells are supplied by the first progenitor cells that develop during the differentiation step. These cells are able to regenerate themselves for a long time, though not quite as long as HSCs.
To ensure that the population of this cell type never runs out, HSCs must occasionally produce a couple of new first progenitors.
During murine embryonic development, however, the situation is different. To build up the system, all mature blood and immune cells develop much more rapidly and almost completely from HSCs.
The researchers were also able to accelerate this process in adult mice by artificially depleting their white blood cells. Under these conditions, HSCs increase the formation of first progenitor cells, which then immediately start supplying new, mature blood cells.
During this process, several hundred times more myeloid cells (thrombocytes, erythrocytes, granulocytes, monocytes) form than long-lived lymphocytes (T cells, B cells, natural killer cells).
“When we transplanted our labeled blood stem cells from the bone marrow into other mice, only a few stem cells were active in the recipients, and many stem cells were lost,” Dr Rodewald noted.
“Our new data therefore show that the findings obtained up until now using transplanted stem cells can surely not be reflective of normal hematopoiesis. On the contrary, transplantation is an exception. This shows how important it is that we actually follow hematopoiesis under normal conditions in a living organism.”
The researchers now plan to use their model to investigate the impact of pathogenic challenges to blood formation; for example, in cancer, cachexia, or infection. This method would also allow them to follow potential aging processes in HSCs as they occur naturally in a living organism. 
in the bone marrow
Scientists have reported a method for equipping mouse hematopoietic stem cells (HSCs) with a fluorescent marker that can be switched on from the outside.
Using this tool, they were able to observe how HSCs mature into blood cells under normal conditions, and they developed a mathematical model of the dynamics of hematopoiesis.
The research suggests the normal process of hematopoiesis differs from what scientists previously assumed when using data from stem cell transplants.
“[A] problem with almost all research on hematopoiesis in past decades is that it has been restricted to experiments in culture or using transplantation into mice,” said study author Hans-Reimer Rodewald, PhD, of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg.
“We have now developed the first model where we can observe the development of a stem cell into a mature blood cell in a living organism.”
The researchers described this model in Nature.
The team genetically modified mice by introducing a protein into their HSCs that sends out a yellow fluorescent signal. This marker can be turned on by administering a reagent. All daughter cells that arise from a cell containing the marker also send out a light signal.
When they turned on the marker in adult mice, the researchers observed that at least a third of a mouse’s HSCs (approximately 5000 cells) produce differentiated progenitor cells.
“This was the first surprise,” said study author Katrin Busch, also of DKFZ. “Until now, scientists had believed that, in the normal state, very few stem cells—only about 10—are actively involved in blood formation.”
The researchers performed a mathematical analysis of these experimental data to provide additional insight into blood stem cell dynamics. They were surprised to find that, under normal conditions, HSCs do not replenish blood cells.
Instead, blood cells are supplied by the first progenitor cells that develop during the differentiation step. These cells are able to regenerate themselves for a long time, though not quite as long as HSCs.
To ensure that the population of this cell type never runs out, HSCs must occasionally produce a couple of new first progenitors.
During murine embryonic development, however, the situation is different. To build up the system, all mature blood and immune cells develop much more rapidly and almost completely from HSCs.
The researchers were also able to accelerate this process in adult mice by artificially depleting their white blood cells. Under these conditions, HSCs increase the formation of first progenitor cells, which then immediately start supplying new, mature blood cells.
During this process, several hundred times more myeloid cells (thrombocytes, erythrocytes, granulocytes, monocytes) form than long-lived lymphocytes (T cells, B cells, natural killer cells).
“When we transplanted our labeled blood stem cells from the bone marrow into other mice, only a few stem cells were active in the recipients, and many stem cells were lost,” Dr Rodewald noted.
“Our new data therefore show that the findings obtained up until now using transplanted stem cells can surely not be reflective of normal hematopoiesis. On the contrary, transplantation is an exception. This shows how important it is that we actually follow hematopoiesis under normal conditions in a living organism.”
The researchers now plan to use their model to investigate the impact of pathogenic challenges to blood formation; for example, in cancer, cachexia, or infection. This method would also allow them to follow potential aging processes in HSCs as they occur naturally in a living organism.
in the bone marrow
Scientists have reported a method for equipping mouse hematopoietic stem cells (HSCs) with a fluorescent marker that can be switched on from the outside.
Using this tool, they were able to observe how HSCs mature into blood cells under normal conditions, and they developed a mathematical model of the dynamics of hematopoiesis.
The research suggests the normal process of hematopoiesis differs from what scientists previously assumed when using data from stem cell transplants.
“[A] problem with almost all research on hematopoiesis in past decades is that it has been restricted to experiments in culture or using transplantation into mice,” said study author Hans-Reimer Rodewald, PhD, of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg.
“We have now developed the first model where we can observe the development of a stem cell into a mature blood cell in a living organism.”
The researchers described this model in Nature.
The team genetically modified mice by introducing a protein into their HSCs that sends out a yellow fluorescent signal. This marker can be turned on by administering a reagent. All daughter cells that arise from a cell containing the marker also send out a light signal.
When they turned on the marker in adult mice, the researchers observed that at least a third of a mouse’s HSCs (approximately 5000 cells) produce differentiated progenitor cells.
“This was the first surprise,” said study author Katrin Busch, also of DKFZ. “Until now, scientists had believed that, in the normal state, very few stem cells—only about 10—are actively involved in blood formation.”
The researchers performed a mathematical analysis of these experimental data to provide additional insight into blood stem cell dynamics. They were surprised to find that, under normal conditions, HSCs do not replenish blood cells.
Instead, blood cells are supplied by the first progenitor cells that develop during the differentiation step. These cells are able to regenerate themselves for a long time, though not quite as long as HSCs.
To ensure that the population of this cell type never runs out, HSCs must occasionally produce a couple of new first progenitors.
During murine embryonic development, however, the situation is different. To build up the system, all mature blood and immune cells develop much more rapidly and almost completely from HSCs.
The researchers were also able to accelerate this process in adult mice by artificially depleting their white blood cells. Under these conditions, HSCs increase the formation of first progenitor cells, which then immediately start supplying new, mature blood cells.
During this process, several hundred times more myeloid cells (thrombocytes, erythrocytes, granulocytes, monocytes) form than long-lived lymphocytes (T cells, B cells, natural killer cells).
“When we transplanted our labeled blood stem cells from the bone marrow into other mice, only a few stem cells were active in the recipients, and many stem cells were lost,” Dr Rodewald noted.
“Our new data therefore show that the findings obtained up until now using transplanted stem cells can surely not be reflective of normal hematopoiesis. On the contrary, transplantation is an exception. This shows how important it is that we actually follow hematopoiesis under normal conditions in a living organism.”
The researchers now plan to use their model to investigate the impact of pathogenic challenges to blood formation; for example, in cancer, cachexia, or infection. This method would also allow them to follow potential aging processes in HSCs as they occur naturally in a living organism.