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Credit: John Perry
A protein known as GPI-80 is integral to the self-renewal of hematopoietic stem cells (HSCs) during human development, investigators have reported in Cell Stem Cell.
The team says this discovery lays the groundwork for researchers to generate HSCs in the lab that better mirror HSCs in their natural environment.
This could lead to improved therapies for hematologic disorders by enabling the creation of patient-specific HSCs for transplantation.
In a 5-year study, Hanna Katri Annikki Mikkola, MD, PhD, of the University of California, Los Angeles, and her colleagues investigated a unique HSC surface protein called GPI-80.
They found that GPI-80 is produced by a subpopulation of human fetal hematopoietic stem/progenitor cells (HSPCs)—the only group of cells that could self-renew and differentiate into various blood cell types.
The investigators also found that this subpopulation—CD34+CD38lo/-CD90+GPI-80+ HSPCs—was the sole population able to permanently integrate into and thrive within the blood system of a recipient mouse.
Dr Mikkola and her colleagues further discovered that GPI-80 identifies human HSPCs during multiple phases of development and migration.
These include the early first trimester of fetal development, when newly generated HSCs can be found in the placenta, and the second trimester, when HSCs are actively replicating in the fetal liver and the fetal bone marrow.
“We found that whatever HSC niche we investigated, we could use GPI-80 as the best determinant to find the stem cell as it was being generated or colonized different hematopoietic tissues,” Dr Mikkola said.
“Moreover, loss of GPI-80 caused the stem cells to differentiate. This essentially tells us that GPI-80 must be present to make HSCs. We now have a very unique marker for investigating how human hematopoietic cells develop, migrate, and function.”
Dr Mikkola’s team is exploring different stages of human HSC development and pluripotent stem cell differentiation based on the GPI-80 marker and comparing how HSCs are being generated in vitro and in vivo.
The group says this paves the way for scientists to redirect pluripotent stem cells into patient-specific HSCs for transplantation into a patient without the need to find a suitable donor.
“Now that we can use GPI-80 as a marker to isolate the human hematopoietic stem cell at different stages of development, this can serve as a guide for identifying and overcoming the barriers to making human HSCs in vitro, which has never been done successfully,” Dr Mikkola said.
“We can now better understand the missing molecular elements that in vitro-derived cells don’t have, which is critical to fulfilling the functional and safety criteria for transplantation to patients.” 
Credit: John Perry
A protein known as GPI-80 is integral to the self-renewal of hematopoietic stem cells (HSCs) during human development, investigators have reported in Cell Stem Cell.
The team says this discovery lays the groundwork for researchers to generate HSCs in the lab that better mirror HSCs in their natural environment.
This could lead to improved therapies for hematologic disorders by enabling the creation of patient-specific HSCs for transplantation.
In a 5-year study, Hanna Katri Annikki Mikkola, MD, PhD, of the University of California, Los Angeles, and her colleagues investigated a unique HSC surface protein called GPI-80.
They found that GPI-80 is produced by a subpopulation of human fetal hematopoietic stem/progenitor cells (HSPCs)—the only group of cells that could self-renew and differentiate into various blood cell types.
The investigators also found that this subpopulation—CD34+CD38lo/-CD90+GPI-80+ HSPCs—was the sole population able to permanently integrate into and thrive within the blood system of a recipient mouse.
Dr Mikkola and her colleagues further discovered that GPI-80 identifies human HSPCs during multiple phases of development and migration.
These include the early first trimester of fetal development, when newly generated HSCs can be found in the placenta, and the second trimester, when HSCs are actively replicating in the fetal liver and the fetal bone marrow.
“We found that whatever HSC niche we investigated, we could use GPI-80 as the best determinant to find the stem cell as it was being generated or colonized different hematopoietic tissues,” Dr Mikkola said.
“Moreover, loss of GPI-80 caused the stem cells to differentiate. This essentially tells us that GPI-80 must be present to make HSCs. We now have a very unique marker for investigating how human hematopoietic cells develop, migrate, and function.”
Dr Mikkola’s team is exploring different stages of human HSC development and pluripotent stem cell differentiation based on the GPI-80 marker and comparing how HSCs are being generated in vitro and in vivo.
The group says this paves the way for scientists to redirect pluripotent stem cells into patient-specific HSCs for transplantation into a patient without the need to find a suitable donor.
“Now that we can use GPI-80 as a marker to isolate the human hematopoietic stem cell at different stages of development, this can serve as a guide for identifying and overcoming the barriers to making human HSCs in vitro, which has never been done successfully,” Dr Mikkola said.
“We can now better understand the missing molecular elements that in vitro-derived cells don’t have, which is critical to fulfilling the functional and safety criteria for transplantation to patients.”
Credit: John Perry
A protein known as GPI-80 is integral to the self-renewal of hematopoietic stem cells (HSCs) during human development, investigators have reported in Cell Stem Cell.
The team says this discovery lays the groundwork for researchers to generate HSCs in the lab that better mirror HSCs in their natural environment.
This could lead to improved therapies for hematologic disorders by enabling the creation of patient-specific HSCs for transplantation.
In a 5-year study, Hanna Katri Annikki Mikkola, MD, PhD, of the University of California, Los Angeles, and her colleagues investigated a unique HSC surface protein called GPI-80.
They found that GPI-80 is produced by a subpopulation of human fetal hematopoietic stem/progenitor cells (HSPCs)—the only group of cells that could self-renew and differentiate into various blood cell types.
The investigators also found that this subpopulation—CD34+CD38lo/-CD90+GPI-80+ HSPCs—was the sole population able to permanently integrate into and thrive within the blood system of a recipient mouse.
Dr Mikkola and her colleagues further discovered that GPI-80 identifies human HSPCs during multiple phases of development and migration.
These include the early first trimester of fetal development, when newly generated HSCs can be found in the placenta, and the second trimester, when HSCs are actively replicating in the fetal liver and the fetal bone marrow.
“We found that whatever HSC niche we investigated, we could use GPI-80 as the best determinant to find the stem cell as it was being generated or colonized different hematopoietic tissues,” Dr Mikkola said.
“Moreover, loss of GPI-80 caused the stem cells to differentiate. This essentially tells us that GPI-80 must be present to make HSCs. We now have a very unique marker for investigating how human hematopoietic cells develop, migrate, and function.”
Dr Mikkola’s team is exploring different stages of human HSC development and pluripotent stem cell differentiation based on the GPI-80 marker and comparing how HSCs are being generated in vitro and in vivo.
The group says this paves the way for scientists to redirect pluripotent stem cells into patient-specific HSCs for transplantation into a patient without the need to find a suitable donor.
“Now that we can use GPI-80 as a marker to isolate the human hematopoietic stem cell at different stages of development, this can serve as a guide for identifying and overcoming the barriers to making human HSCs in vitro, which has never been done successfully,” Dr Mikkola said.
“We can now better understand the missing molecular elements that in vitro-derived cells don’t have, which is critical to fulfilling the functional and safety criteria for transplantation to patients.”