Differentiation of granulocytic and monocytic progenitor cells

Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Animal cell – per se – expressing immunoglobulin – antibody – or...

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435325, 435372, C12N 500, C12N 506, C12N 508

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active

060965401

ABSTRACT:
The present invention demonstrates that M-CSF responsiveness and the M-CSFR expression can be used to discriminate monocytic and granulocytic cells within a population of cells which strongly expresses the CD34 antigen (CD34.sup.hi). Briefly, the method comprises isolating phenotypically and functionally defined CD34.sup.+ subsets, and staining with anti-M-CSFR monoclonal antibodies to measure expression on these primitive progenitors and cells committed to the granulocytic and monocytic lineages, based upon expression of M-CSFR. CD34.sup.hi M-CSFR.sup.hi cells are highly clonogenic and approximately 70% of the colonies are CFU-M (monocytic), whereas less than 20% were CFU-G (granulocytic). In contrast, CD34.sup.hi cells that were positive for the granulo-monocytic marker CD64 and negative for the M-CSFR contained high frequencies of 91% pure CFU-Gs. After 60 h in culture, CD34.sup.hi M-CSFR.sup.hi cells developed into distinct populations of M-CSFR.sup.hi and M-CSFR.sup.lo cells. These two populations gave rise almost exclusively to monocytes and granulocytes, respectively. This result demonstrates that M-CSF target specificity among human hematopoietic progenitor cells is determined by lineage-specific regulation of the M-CSFR and demonstrate that M-CSFR is a useful marker to discriminate CFU-Ms from CFU-Gs.

REFERENCES:
Olweus et al. Blood 85: 2402-2413 (1995).
Zhang et al. Mol. Cell. Biol 14:373-381 (1994).
Gliniak et al. Cell 63: 1073-1083 (1990).

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