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TISSUE-SPECIFIC STEM CELLS

Differential Amplification of Murine Bipotent Megakaryocytic/Erythroid Progenitor and Precursor Cells During Recovery from Acute and Chronic Erythroid Stress

^a Istituto Superiore di Sanità, Rome, Italy;
^b Department of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, California, USA;
^c School of Natural Sciences, University of California, Merced, California, USA;
^d Department of Hematology, University of Florence, Florence, Italy;
^e Department of Pathology and Cancer Center, University of Illinois at Chicago, Chicago, Illinois, USA

Key Words. Erythroid progenitors • Megakaryocytic progenitors • Erythroid stress • GATA-1 • Phenylhydrazine

Correspondence: Anna Rita Migliaccio, Ph.D., Istituto Superiore Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Telephone: 39-06-49902690; Fax: 39-06-49902530; e-mail: migliar{at}iss.it

Two murine bipotent erythroid/megakaryocytic cells, the progenitor (MEP) and precursor (PEM) cells, recently have been identified on the basis of the phenotypes of lin^negc-kit^posSca-1^neg CD16/CD32^lowCD34^low and TER119^pos4A5^pos or 2D5^pos, respectively. However, the functional relationship between these two subpopulations and their placement in the hemopoietic hierarchy is incompletely understood. We compared the biological properties of these subpopulations in marrow and spleen of mice with and without acute or chronic erythroid stress. MEP cells, but not PEM cells, express c-kit, respond to stem cell factor in vitro, and form spleen colonies in vivo. PEM cells comprise up to 50%–70% of the cells in BFU-E–derived colonies but are not present among the progeny of purified MEP cells cultured under erythroid and megakaryocytic permissive conditions. PEM cells increase 10- to 20-fold under acute and chronic stress, whereas MEP cell increases (21%–84%) are observed only in acutely stressed animals. These data suggest that MEP and PEM cells represent distinct cell populations that may exist in an upstream-downstream differentiation relationship under conditions of stress. Whereas the dynamics of both populations are altered by stress induction, the differential response to acute and chronic stress suggests different regulatory mechanisms. A model describing the relationship between MEP, PEM, and common myeloid progenitor cells is presented.

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