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Developmental changes in pluripotent hematopoietic progenitors
1Department of Pediatrics, University of Utah School of Medicine, Salt Lake City 84132.
Insights
Hematopoietic stem cell proliferation differs between fetal and adult rats. Fetal rats show higher blood stem cell concentrations but lower overall body stem cells and limited response to growth factors, impacting progeny production.
Area of Science:
- Hematology
- Developmental Biology
- Stem Cell Research
Background:
- Pluripotent hematopoietic progenitor cells (CFU-GEMM) are crucial for blood cell formation.
- Understanding their distribution and cell-cycle characteristics across different developmental stages is vital for comprehending hematopoiesis.
Purpose of the Study:
- To compare the number and cell-cycle characteristics of pluripotent hematopoietic progenitor cells (CFU-GEMM) in rats at various prenatal and postnatal ages.
- To investigate the proliferative potential and response to Interleukin 3 (IL-3) in fetal versus adult CFU-GEMM.
Main Methods:
- Quantification of CFU-GEMM in blood, liver, spleen, and bone marrow across different rat ages.
- Assessment of cell-cycle status using tritiated thymidine suicide assay.
- Evaluation of CFU-GEMM response to Interleukin 3 (IL-3) stimulation.
Main Results:
- Fetal and neonatal rats exhibit significantly higher blood CFU-GEMM concentrations compared to adult rats.
- Despite higher blood concentrations, fetal rats have a lower total body pool of CFU-GEMM per gram of body weight than adults.
- Fetal CFU-GEMM show a high rate of cell-cycle activity (over 90% suicide), while adult CFU-GEMM have a low rate (2%).
- Mature rat CFU-GEMM show a significant increase in proliferation after IL-3 incubation, unlike fetal CFU-GEMM.
Conclusions:
- Developmental stage significantly influences the distribution, cell-cycle activity, and responsiveness of hematopoietic progenitor cells.
- The high cell-cycle activity and lack of IL-3 response in fetal CFU-GEMM may explain the limited capacity for increased progeny production in neonatal subjects.
- These findings provide insights into the regulation of hematopoiesis during development and potential limitations in neonatal immune responses.
Abstract:
In rats of various prenatal and postnatal ages, the number of pluripotent hematopoietic progenitor cells (CFU-GEMM) in the blood, liver, spleen and bone marrow was determined, and their cell-cycle characteristics compared. Similar to human neonates, fetal and neonatal rats had a much higher concentration of CFU-GEMM in the blood than did mature animals (2060-8320 CFU-GEMM/ml blood at 15 days gestation vs. 20-120/ml at six weeks of age, P less than 0.001). However, the total body pool of CFU-GEMM/g body weight was significantly less in fetal animals than in adults (2010 CFU-GEMM/g, range 850-2650/g at 20 days gestation vs. 10 550/g, range 7900-14,900/g at 6 weeks, P less than 0.001). The proportion of CFU-GEMM killed by tritiated thymidine was 2% (0-12%) in adults rats, whereas younger animals had progressively higher rates, reaching over 90% (68-100) in fetal animals (P less than 0.001). Following incubation with Interleukin 3 (IL-3), the thymidine suicide rate of CFU-GEMM from mature rates increased significantly (from 4 +/- 3% to 53 +/- 4%, P less than 0.01), but no increase was detected in CFU-GEMM from fetal rats. These features might contribute to the limited capacity of neonatal subjects to significantly increase production of the progeny of CFU-GEMM.