Clonal stability of blood cell lineages indicated by X-chromosomal transcriptional polymorphism

• Type of Material: Article
• Authors: Josef T. Prchal, University of Alabama at Birmingham; Jaroslav F. Prchal, McGill University; Monika Belickova, University of Alabama at Birmingham; Shande Chen, University of Alabama at Birmingham; Yongli Guan, University of Alabama at Birmingham; G. Larry Gartland, University of Alabama at Birmingham; Max Cooper, Emory University
• Language: English
• Date: 1996-02-01
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © Rockefeller University Press
• Final Published Version (URL): http://dx.doi.org/10.1084/jem.183.2.561
• Title of Journal or Parent Work: Journal of Experimental Medicine
• ISSN: 0022-1007
• Volume: 183
• Issue: 2
• Start Page: 561
• End Page: 567
• Grant/Funding Information: This work was supported, in part, by the Veterans Administration Hospital (VAH) Merit grant (J. T. Prchal), U.S. Public Health Service grants t(O1 HL-51650 and HL-50077 (J. T. Prchal) and AI-39816 and AI34568 (M. D. Cooper). M. D. Cooper is an Investigator of the Howard Hughes Medical Institute.
• Keywords: RNA; Research & Experimental Medicine; Hematology; MARROW; ORIGIN; HEMATOPOIETIC STEM-CELLS; G6PD; Science & Technology; Immunology; INACTIVATION PATTERNS; Life Sciences & Biomedicine
• Research Categories: Biology, Cell; Health Sciences, Immunology

Abstract

The idea that stem cells oscillate between a state of activity and dormancy, thereby giving rise to differentiating progeny either randomly or in orderly clonal succession, has important implications for understanding normal hematopoiesis and blood cell dyscrasias. The degree of clonal stability in individuals also has practical implications for the evaluation of clonal lymphomyeloproliferative diseases. To evaluate the clonality pattern of the different types of blood cells as a function of time we have validated the applicability, sensitivity, and reproducibility of a thermostable ligase reactions to detect transcripts of the G6PD allele on the active X-chromosome in normal heterozygous females. While the ratio of the two X-chromosome-derived allelic transcripts varied widely among hemopoietic and nonhemopoietic tissues in a given individual, this allelic ratio was virtually identical in all types of mature myeloid and lymphoid cells. Longitudinal studies indicated constancy of the G6PD allelic ratio in blood cells over a 912-d period of observation in healthy females. The individual variability observed in this allelic ratio suggests that the progeny of a relatively small number of original embryonic hemopoietic stem cells, approximately eight, contribute to the sustained production of all types of blood cells in healthy individuals.