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Updated: Aug 23, 2026
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
Published on: February 21, 2018
G-CSF induced progenitor mobilization in mice with PIGA- blood cells
Bing Han1, Jacqueline Unsinger, Fulu Liu
1Division of Hematology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Insights
In paroxysmal nocturnal hemoglobinuria (PNH), a lack of glycosyl phosphatidylinositol (GPI)-linked proteins doesn't retain progenitor cells in bone marrow. Normal progenitor cell circulation in PNH likely involves the bone marrow microenvironment, not just GPI-linked proteins.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Paroxysmal nocturnal hemoglobinuria (PNH) involves blood cells deficient in glycosyl phosphatidylinositol (GPI)-anchored proteins due to PIGA gene mutations.
- Previous research suggested GPI-linked proteins regulate progenitor cell trafficking from bone marrow to peripheral blood.
Purpose of the Study:
- To investigate the role of GPI-linked proteins in progenitor cell trafficking.
- To test if GPI-linked protein deficiency causes progenitor cell retention in bone marrow.
Main Methods:
- Studied progenitor cells in bone marrow, spleen, and peripheral blood of genetically engineered mice lacking GPI-linked proteins (LF mice) and wild-type mice.
- Administered G-CSF to assess progenitor cell response.
Main Results:
- LF and wild-type mice showed comparable progenitor cell numbers in bone marrow, spleen, and peripheral blood.
- G-CSF increased circulating progenitors, but the proportion of PIGA-deficient cells remained consistent across tissues in LF mice.
- Lack of GPI-linked proteins did not lead to progenitor cell retention in bone marrow.
Conclusions:
- The absence of GPI-linked proteins alone does not cause progenitor cell retention in the bone marrow under normal conditions.
- Preferential circulation of normal progenitor cells in PNH patients likely requires additional factors from the altered bone marrow microenvironment.
Objective:
In patients with paroxysmal nocturnal hemoglobinuria (PNH) a proportion of blood cells are deficient in glycosyl phosphatidylinositol (GPI) anchored proteins due to a mutation in the PIGA gene. Previous studies showed that in PNH the majority of circulating early progenitor cells were normal but after G-CSF were mainly, of the PNH phenotype. This suggested that GPI-linked proteins contribute to the regulation of progenitor trafficking from bone marrow to peripheral blood.
Methods:
To test this hypothesis we studied progenitor cells in bone marrow, spleen, and peripheral blood in response to G-CSF in mice genetically engineered to have a proportion of blood cells deficient in GPI-linked proteins (LF mice).
Results:
In contrast to humans, LF and wild-type mice have comparable numbers of progenitor cells in bone marrow, spleen, and peripheral blood. Similarly, in LF mice the proportion of PIGA- progenitor cells in peripheral blood corresponds the proportion of PIGA- progenitor cells measured in bone marrow and spleen. After G-CSF the number of circulating progenitors significantly increased but the proportion of PIGA- cells remained the same in peripheral blood,bone marrow, and spleen.
Conclusions:
Our data indicate that under basal laboratory conditions the lack of GPI-linked protein does not cause a retention of progenitor cells in the bone marrow. This implies that the preferential circulation of normal progenitor cells in patients with PNH requires an additional component that most likely is provided by the altered microenvironment of the underlying bone marrow failure.
