Hematopoeitic progenitor cell emergence em fetal liver and migration to bone marrow during murine ontogeny

P. M. Wolber, Edward Srour, S. Michael, E. Leonard, Mervin Yoder

Research output: Contribution to journalArticle

Abstract

Hematopoeitic progenitor cells (HPC) are believed to migrate from murine fetal liver (FL) to the neonatal bone marrow (BM). It is unclear if the entire pool of HPC in one tissue migrates and further expands in the seeded tissue. We assessed HPC in FL and BM at different gestational ages. The number of total cells in FL increased steadily throughout gestation. The proportion of CD45+ cells increased from 6.7±1.2% at day (d) 12 postcoitus (pc) to 31.1±3.6% at dig pc (p<0.001). As gestation progressed, FL CD45+ cells expressed CD34 in decreasing proportions (d!2 pc, 69115.6% vs. d!8 pc, 9.7±5.2%; p<0.001). Accordingly, CD45+ cells from maturing FL had decreased clonogenic ability, particularly for CFU-GEMM. This was not solely due to a decrease in HPC frequency among CD45+ cells in more mature mice, since 2.4 times more clonogenic cells were detected among sorted CD45+34+ Sca-l+ cells from d!2 pc FL than in similar cells from adult BM (aBM), suggesting that the former have a higher proliferative potential. This hypothesis was emphasized by these cells' disparate proportion of c-kit expression (d!2 pc FL, 77.7±22.8% vs. aBM, [ 14.9±1.6%). We next examined the colony-forming potential of unfractionated cell ' preparations and calculated the number of colony-forming cells (CFC) present in FL or aBM at various points of maturation. CFU-GM, BFU-E and CFU-GEMM were all present in low numbers in day 12 pc FL, with a total CFC number of <5500 per FL. The number of FL CFC tripled at d!4 pc and subsequently quadrupled at day 16 pc. CFC decreased at day 18 pc, suggesting that migration to the BM microenvironment begins before or at this time. However, after birth, quantifiable CFC persisted in neonatal liver (150 per mouse) for up to 12 days but were found in very low numbers in neonatal BM at this time (<1000 at 12 days versus 150,000 at 90+ days). This lack of a detectable increase in BM CFC to correspond with the decline in FL CFC during ontogeny implies inefficient homing to BM of egressing FL progenitor and stem cells. These resusts also suggest that CFC production in each hematopoietic tissue during ontogeny results from the expansion of a limited number of migrating HPC.

Original languageEnglish
JournalBlood
Volume96
Issue number11 PART I
StatePublished - 2000

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Liver
Bone
Stem Cells
Bone Marrow
Myeloid Progenitor Cells
Tissue
Cell Count
Pregnancy
Granulocyte-Macrophage Progenitor Cells
Erythroid Precursor Cells
Stem cells
Bone Marrow Cells
Gestational Age
Parturition

ASJC Scopus subject areas

  • Hematology

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Hematopoeitic progenitor cell emergence em fetal liver and migration to bone marrow during murine ontogeny. / Wolber, P. M.; Srour, Edward; Michael, S.; Leonard, E.; Yoder, Mervin.

In: Blood, Vol. 96, No. 11 PART I, 2000.

Research output: Contribution to journalArticle

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abstract = "Hematopoeitic progenitor cells (HPC) are believed to migrate from murine fetal liver (FL) to the neonatal bone marrow (BM). It is unclear if the entire pool of HPC in one tissue migrates and further expands in the seeded tissue. We assessed HPC in FL and BM at different gestational ages. The number of total cells in FL increased steadily throughout gestation. The proportion of CD45+ cells increased from 6.7±1.2{\%} at day (d) 12 postcoitus (pc) to 31.1±3.6{\%} at dig pc (p<0.001). As gestation progressed, FL CD45+ cells expressed CD34 in decreasing proportions (d!2 pc, 69115.6{\%} vs. d!8 pc, 9.7±5.2{\%}; p<0.001). Accordingly, CD45+ cells from maturing FL had decreased clonogenic ability, particularly for CFU-GEMM. This was not solely due to a decrease in HPC frequency among CD45+ cells in more mature mice, since 2.4 times more clonogenic cells were detected among sorted CD45+34+ Sca-l+ cells from d!2 pc FL than in similar cells from adult BM (aBM), suggesting that the former have a higher proliferative potential. This hypothesis was emphasized by these cells' disparate proportion of c-kit expression (d!2 pc FL, 77.7±22.8{\%} vs. aBM, [ 14.9±1.6{\%}). We next examined the colony-forming potential of unfractionated cell ' preparations and calculated the number of colony-forming cells (CFC) present in FL or aBM at various points of maturation. CFU-GM, BFU-E and CFU-GEMM were all present in low numbers in day 12 pc FL, with a total CFC number of <5500 per FL. The number of FL CFC tripled at d!4 pc and subsequently quadrupled at day 16 pc. CFC decreased at day 18 pc, suggesting that migration to the BM microenvironment begins before or at this time. However, after birth, quantifiable CFC persisted in neonatal liver (150 per mouse) for up to 12 days but were found in very low numbers in neonatal BM at this time (<1000 at 12 days versus 150,000 at 90+ days). This lack of a detectable increase in BM CFC to correspond with the decline in FL CFC during ontogeny implies inefficient homing to BM of egressing FL progenitor and stem cells. These resusts also suggest that CFC production in each hematopoietic tissue during ontogeny results from the expansion of a limited number of migrating HPC.",
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AU - Srour, Edward

AU - Michael, S.

AU - Leonard, E.

AU - Yoder, Mervin

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AB - Hematopoeitic progenitor cells (HPC) are believed to migrate from murine fetal liver (FL) to the neonatal bone marrow (BM). It is unclear if the entire pool of HPC in one tissue migrates and further expands in the seeded tissue. We assessed HPC in FL and BM at different gestational ages. The number of total cells in FL increased steadily throughout gestation. The proportion of CD45+ cells increased from 6.7±1.2% at day (d) 12 postcoitus (pc) to 31.1±3.6% at dig pc (p<0.001). As gestation progressed, FL CD45+ cells expressed CD34 in decreasing proportions (d!2 pc, 69115.6% vs. d!8 pc, 9.7±5.2%; p<0.001). Accordingly, CD45+ cells from maturing FL had decreased clonogenic ability, particularly for CFU-GEMM. This was not solely due to a decrease in HPC frequency among CD45+ cells in more mature mice, since 2.4 times more clonogenic cells were detected among sorted CD45+34+ Sca-l+ cells from d!2 pc FL than in similar cells from adult BM (aBM), suggesting that the former have a higher proliferative potential. This hypothesis was emphasized by these cells' disparate proportion of c-kit expression (d!2 pc FL, 77.7±22.8% vs. aBM, [ 14.9±1.6%). We next examined the colony-forming potential of unfractionated cell ' preparations and calculated the number of colony-forming cells (CFC) present in FL or aBM at various points of maturation. CFU-GM, BFU-E and CFU-GEMM were all present in low numbers in day 12 pc FL, with a total CFC number of <5500 per FL. The number of FL CFC tripled at d!4 pc and subsequently quadrupled at day 16 pc. CFC decreased at day 18 pc, suggesting that migration to the BM microenvironment begins before or at this time. However, after birth, quantifiable CFC persisted in neonatal liver (150 per mouse) for up to 12 days but were found in very low numbers in neonatal BM at this time (<1000 at 12 days versus 150,000 at 90+ days). This lack of a detectable increase in BM CFC to correspond with the decline in FL CFC during ontogeny implies inefficient homing to BM of egressing FL progenitor and stem cells. These resusts also suggest that CFC production in each hematopoietic tissue during ontogeny results from the expansion of a limited number of migrating HPC.

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