Estimation of the number of hematopoietic precursor cells during fetal mouse development by covariance analysis

Differentiation of hematopoietic precursor cells results in the formation of clonally related descendent cells. Using the mosaic expression of beta-galactosidase in female mouse fetuses heterozygous for an X-linked lacZ transgene, we analyzed the clonal relationship of the hematopoietic progeny. The proportion of beta-galactosidase positive cells for different T- and B-lymphoid and myeloid cell populations was determined at different stages of fetal development. We found excellent correlations of the proportion of beta-galactosidase expressing cells for all hematopoietic lineages confirming that they share a common ancestry. Therefore, it was possible to estimate the number of common precursor cells (PC) based on binomial distribution and covariance analysis of pairs of different hematopoietic cell populations. Our results obtained from hematopoietic cells at 15.5 to 18.5 days of gestation indicated the presence of 15 to 18 lymphoid and 18 to 22 myeloid/lymphoid specific precursor cells. Statistical analysis of the precursor cell numbers showed a trend of increasing numbers that was highly significant. The precursor cell number was inversely related to maturity of the cell populations analyzed; ie, the lowest number of lymphoid and lymphoid/myeloid precursors was calculated when the most mature CD3+ T-cell population was used for comparison. Determination of PC numbers can therefore be used to assess the relative maturity and developmental potential of individual cell populations.

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The Notch Ligand, Jagged-1, Influences the Development of Primitive Hematopoietic Precursor Cells

Blood ◽

10.1182/blood.v91.11.4084.411k05_4084_4091 ◽

1998 ◽

Vol 91 (11) ◽

pp. 4084-4091 ◽

Cited By ~ 7

Author(s):

Barbara Varnum-Finney ◽

Louise E. Purton ◽

Monica Yu ◽

Carolyn Brashem-Stein ◽

David Flowers ◽

...

Keyword(s):

Fetal Liver ◽

Precursor Cells ◽

Precursor Cell ◽

Cell Populations ◽

Notch 1 ◽

Notch Ligand ◽

Murine Bone Marrow ◽

Ligand Interactions ◽

Hematopoietic Precursor

We examined the expression of two members of theNotch family, Notch-1 and Notch-2, and one Notch ligand, Jagged-1, in hematopoietic cells. Both Notch-1 and Notch-2 were detected in murine marrow precursors (Lin−Sca-1+c-kit+). The Notch ligand, Jagged-1, was not detected in whole marrow or in precursors. However, Jagged-1 was seen in cultured primary murine fetal liver stroma, cultured primary murine bone marrow stroma, and in stromal cell lines. These results indicate a potential role for Notch-Notch ligand interactions in hematopoiesis. To further test this possibility, the effect of Jagged-1 on murine marrow precursor cells was assessed by coculturing sorted precursor cells (Lin−Sca-1+c-kit+) with a 3T3 cell layer that expressed human Jagged-1 or by incubating sorted precursors with beads coated with the purified extracellular domain of human Jagged-1 (Jagged-1ext). We found that Jagged-1, presented both on the cell surface and on beads, promoted a twofold to threefold increase in the formation of primitive precursor cell populations. These results suggest a potential use for Notch ligands in expanding precursor cell populations in vitro.

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Ia antigen is a differentiation marker on human eosinophils

Blood ◽

10.1182/blood.v56.1.11.11 ◽

1980 ◽

Vol 56 (1) ◽

pp. 11-14 ◽

Cited By ~ 10

Author(s):

HP Koeffler ◽

R Billing ◽

AM Levine ◽

DW Golde

Keyword(s):

Precursor Cells ◽

Precursor Cell ◽

Human Eosinophil ◽

Ia Antigen ◽

Hematopoietic Precursor Cells ◽

La Antigen ◽

Hematopoietic Precursor ◽

Differentiation Marker ◽

Early Human

Abstract Evidence suggests that the “la-like” or antigen is a differentiation marker that is expressed on early human hematopoietic precursor cells, but is absent on their mature progeny. The eosinophil precursor cell (CFU-EO) is distinct from the granulocyte-monocyte colon-forming cell (CFU-C). We provide data that indicate that the ia antigen is expressed on the human eosinophil colony-forming cells and is absent on mature eosinophils. All CFU-EO were inhibited in the presence of rabbit la antiserum at a titer of 1:30. Cytotoxicity was complement-dependent. The metamyelocytic eosinophil and more mature eosinophil forms did not express the la antigen.

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Ia antigen is a differentiation marker on human eosinophils

Blood ◽

10.1182/blood.v56.1.11.bloodjournal56111 ◽

1980 ◽

Vol 56 (1) ◽

pp. 11-14 ◽

Cited By ~ 1

Author(s):

HP Koeffler ◽

R Billing ◽

AM Levine ◽

DW Golde

Keyword(s):

Precursor Cells ◽

Precursor Cell ◽

Human Eosinophil ◽

Ia Antigen ◽

Hematopoietic Precursor Cells ◽

La Antigen ◽

Hematopoietic Precursor ◽

Differentiation Marker ◽

Early Human

Evidence suggests that the “la-like” or antigen is a differentiation marker that is expressed on early human hematopoietic precursor cells, but is absent on their mature progeny. The eosinophil precursor cell (CFU-EO) is distinct from the granulocyte-monocyte colon-forming cell (CFU-C). We provide data that indicate that the ia antigen is expressed on the human eosinophil colony-forming cells and is absent on mature eosinophils. All CFU-EO were inhibited in the presence of rabbit la antiserum at a titer of 1:30. Cytotoxicity was complement-dependent. The metamyelocytic eosinophil and more mature eosinophil forms did not express the la antigen.

Download Full-text

The Notch Ligand, Jagged-1, Influences the Development of Primitive Hematopoietic Precursor Cells

Blood ◽

10.1182/blood.v91.11.4084 ◽

1998 ◽

Vol 91 (11) ◽

pp. 4084-4091 ◽

Cited By ~ 246

Author(s):

Barbara Varnum-Finney ◽

Louise E. Purton ◽

Monica Yu ◽

Carolyn Brashem-Stein ◽

David Flowers ◽

...

Keyword(s):

Fetal Liver ◽

Precursor Cells ◽

Precursor Cell ◽

Cell Populations ◽

Notch 1 ◽

Notch Ligand ◽

Murine Bone Marrow ◽

Ligand Interactions ◽

Hematopoietic Precursor

Abstract We examined the expression of two members of theNotch family, Notch-1 and Notch-2, and one Notch ligand, Jagged-1, in hematopoietic cells. Both Notch-1 and Notch-2 were detected in murine marrow precursors (Lin−Sca-1+c-kit+). The Notch ligand, Jagged-1, was not detected in whole marrow or in precursors. However, Jagged-1 was seen in cultured primary murine fetal liver stroma, cultured primary murine bone marrow stroma, and in stromal cell lines. These results indicate a potential role for Notch-Notch ligand interactions in hematopoiesis. To further test this possibility, the effect of Jagged-1 on murine marrow precursor cells was assessed by coculturing sorted precursor cells (Lin−Sca-1+c-kit+) with a 3T3 cell layer that expressed human Jagged-1 or by incubating sorted precursors with beads coated with the purified extracellular domain of human Jagged-1 (Jagged-1ext). We found that Jagged-1, presented both on the cell surface and on beads, promoted a twofold to threefold increase in the formation of primitive precursor cell populations. These results suggest a potential use for Notch ligands in expanding precursor cell populations in vitro.

Download Full-text