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allows scientists to identify
differences in blood cell origin
Credit: Camargo Lab
By developing a tracking system for stem cells, researchers may have discovered previously unrecognized features of hematopoiesis.
Their work suggests the main drivers of steady-state hematopoiesis are not hematopoietic stem cells (HSCs) but their less pluripotent descendants, progenitor cells.
The team speculates that stable populations of long-lived progenitor cells are responsible for giving rise to specific blood cell types, while HSCs likely act as essential reserves.
The research, published in Nature, indicates that progenitor cells could be just as valuable as HSCs for blood regeneration therapies.
The work challenges what textbooks have long read: that HSCs maintain the day-to-day renewal of blood, a conclusion drawn from their importance in re-establishing blood cell populations after bone marrow transplants.
Due to a lack of tools to study how blood forms in a normal context, no one was able to track the origin of blood cells without doing a transplant.
Fernando Camargo, PhD, of Boston Children’s Hospital in Massachusetts, and his colleagues addressed this problem with a tool that generates a unique barcode in the DNA of all HSCs and their progenitor cells in a mouse.
When a tagged cell divides, all of its descendant cells possess the same barcode. This biological inventory system makes it possible to determine the number of HSCs/progenitors being used to make blood and how long they live, as well as answer fundamental questions about where individual blood cells come from.
“There’s never been such a robust experimental method that could allow people to look at lineage relationships between mature cell types in the body without doing transplantation,” said study author Jianlong Sun, PhD, also of Boston Children’s Hospital.
“One of the major directions we can now go is to revisit the entire blood cell hierarchy and see how the current knowledge holds true when we use this internal labeling system.”
“People have tried using viruses to tag blood cells in the past, but the cells needed to be taken out of the body, infected, and re-transplanted, which raised a number of issues,” Dr Camargo noted. “I wanted to figure out a way to label blood cells inside of the body, and the best idea I had was to use mobile genetic elements called transposons.”
A transposon is a piece of genetic code that can jump to a random point in DNA when exposed to the enzyme transposase. Dr Camargo’s approach works using transgenic mice that possess a single fish-derived transposon in all of their blood cells.
When one of these mice is exposed to transposase, each of its blood cells’ transposons changes location. The location in the DNA where a transposon moves acts as an individual cell’s barcode, so that if the mouse’s blood is taken a few months later, any cell with the same transposon location can be linked back to its parent cell.
Now, the researchers are planning to explore more applications for their barcode tool.
“We are also tremendously excited to use this tool to barcode and track descendants of different stem cells or progenitor cells for a range of conditions, from aging to the normal immune response,” Dr Sun said.
“We first used this technology for blood analysis. However, this system can also help address basic questions about cell populations in solid tissue. You can imagine being able to look at tumor progression or identify the precise origins of cancer cells that have broken off from a tumor and are now circulating in the blood.” 
allows scientists to identify
differences in blood cell origin
Credit: Camargo Lab
By developing a tracking system for stem cells, researchers may have discovered previously unrecognized features of hematopoiesis.
Their work suggests the main drivers of steady-state hematopoiesis are not hematopoietic stem cells (HSCs) but their less pluripotent descendants, progenitor cells.
The team speculates that stable populations of long-lived progenitor cells are responsible for giving rise to specific blood cell types, while HSCs likely act as essential reserves.
The research, published in Nature, indicates that progenitor cells could be just as valuable as HSCs for blood regeneration therapies.
The work challenges what textbooks have long read: that HSCs maintain the day-to-day renewal of blood, a conclusion drawn from their importance in re-establishing blood cell populations after bone marrow transplants.
Due to a lack of tools to study how blood forms in a normal context, no one was able to track the origin of blood cells without doing a transplant.
Fernando Camargo, PhD, of Boston Children’s Hospital in Massachusetts, and his colleagues addressed this problem with a tool that generates a unique barcode in the DNA of all HSCs and their progenitor cells in a mouse.
When a tagged cell divides, all of its descendant cells possess the same barcode. This biological inventory system makes it possible to determine the number of HSCs/progenitors being used to make blood and how long they live, as well as answer fundamental questions about where individual blood cells come from.
“There’s never been such a robust experimental method that could allow people to look at lineage relationships between mature cell types in the body without doing transplantation,” said study author Jianlong Sun, PhD, also of Boston Children’s Hospital.
“One of the major directions we can now go is to revisit the entire blood cell hierarchy and see how the current knowledge holds true when we use this internal labeling system.”
“People have tried using viruses to tag blood cells in the past, but the cells needed to be taken out of the body, infected, and re-transplanted, which raised a number of issues,” Dr Camargo noted. “I wanted to figure out a way to label blood cells inside of the body, and the best idea I had was to use mobile genetic elements called transposons.”
A transposon is a piece of genetic code that can jump to a random point in DNA when exposed to the enzyme transposase. Dr Camargo’s approach works using transgenic mice that possess a single fish-derived transposon in all of their blood cells.
When one of these mice is exposed to transposase, each of its blood cells’ transposons changes location. The location in the DNA where a transposon moves acts as an individual cell’s barcode, so that if the mouse’s blood is taken a few months later, any cell with the same transposon location can be linked back to its parent cell.
Now, the researchers are planning to explore more applications for their barcode tool.
“We are also tremendously excited to use this tool to barcode and track descendants of different stem cells or progenitor cells for a range of conditions, from aging to the normal immune response,” Dr Sun said.
“We first used this technology for blood analysis. However, this system can also help address basic questions about cell populations in solid tissue. You can imagine being able to look at tumor progression or identify the precise origins of cancer cells that have broken off from a tumor and are now circulating in the blood.”
allows scientists to identify
differences in blood cell origin
Credit: Camargo Lab
By developing a tracking system for stem cells, researchers may have discovered previously unrecognized features of hematopoiesis.
Their work suggests the main drivers of steady-state hematopoiesis are not hematopoietic stem cells (HSCs) but their less pluripotent descendants, progenitor cells.
The team speculates that stable populations of long-lived progenitor cells are responsible for giving rise to specific blood cell types, while HSCs likely act as essential reserves.
The research, published in Nature, indicates that progenitor cells could be just as valuable as HSCs for blood regeneration therapies.
The work challenges what textbooks have long read: that HSCs maintain the day-to-day renewal of blood, a conclusion drawn from their importance in re-establishing blood cell populations after bone marrow transplants.
Due to a lack of tools to study how blood forms in a normal context, no one was able to track the origin of blood cells without doing a transplant.
Fernando Camargo, PhD, of Boston Children’s Hospital in Massachusetts, and his colleagues addressed this problem with a tool that generates a unique barcode in the DNA of all HSCs and their progenitor cells in a mouse.
When a tagged cell divides, all of its descendant cells possess the same barcode. This biological inventory system makes it possible to determine the number of HSCs/progenitors being used to make blood and how long they live, as well as answer fundamental questions about where individual blood cells come from.
“There’s never been such a robust experimental method that could allow people to look at lineage relationships between mature cell types in the body without doing transplantation,” said study author Jianlong Sun, PhD, also of Boston Children’s Hospital.
“One of the major directions we can now go is to revisit the entire blood cell hierarchy and see how the current knowledge holds true when we use this internal labeling system.”
“People have tried using viruses to tag blood cells in the past, but the cells needed to be taken out of the body, infected, and re-transplanted, which raised a number of issues,” Dr Camargo noted. “I wanted to figure out a way to label blood cells inside of the body, and the best idea I had was to use mobile genetic elements called transposons.”
A transposon is a piece of genetic code that can jump to a random point in DNA when exposed to the enzyme transposase. Dr Camargo’s approach works using transgenic mice that possess a single fish-derived transposon in all of their blood cells.
When one of these mice is exposed to transposase, each of its blood cells’ transposons changes location. The location in the DNA where a transposon moves acts as an individual cell’s barcode, so that if the mouse’s blood is taken a few months later, any cell with the same transposon location can be linked back to its parent cell.
Now, the researchers are planning to explore more applications for their barcode tool.
“We are also tremendously excited to use this tool to barcode and track descendants of different stem cells or progenitor cells for a range of conditions, from aging to the normal immune response,” Dr Sun said.
“We first used this technology for blood analysis. However, this system can also help address basic questions about cell populations in solid tissue. You can imagine being able to look at tumor progression or identify the precise origins of cancer cells that have broken off from a tumor and are now circulating in the blood.”