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Observations of Residual Differentiation Potential during Lineage Commitment
Author(s) -
SLAYTON WILLIAM B.,
MOJICA MARILUZ P.,
PIERCE L. JEANNE,
SPANGRUDE GERALD J.
Publication year - 2001
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2001.tb03585.x
Subject(s) - haematopoiesis , progenitor cell , biology , stem cell , myeloid , cd34 , immunology , multipotent stem cell , hemoglobin , lineage (genetic) , microbiology and biotechnology , genetics , gene , biochemistry
A bstract : We have recently described a subset of the multipotent progenitor pool that contains a common lymphoid progenitor. This subset of cells is lineage negative and expresses c‐kit and Sca‐1, but lacks expression of Thy 1.1 (Thy neg ). Based on the observation that lethally irradiated mice transplanted with these cells die from anemia unless supported with competitor marrow, we hypothesized that these progenitors lacked erythroid potential. We analyzed the erythroid potential of these cells by transplanting them into mice allelic at the hemoglobin locus and compared their erythroid potential with the Thy‐1.1 low (Thy low ) subset that contains hematopoietic stem cells. We also performed CFU‐C assays in methylcellulose containing recombinant cytokines and determined erythroid contribution to colonies using in situ benzidine staining. Donor‐derived hemoglobin was observed following transplant of Thy neg cells, even though 19 of 20 of these animals died from anemia. In contrast, recipients of Thy low cells showed complete donor‐derived engraftment 30 days following transplant. While approximately 60% of day 4 colonies derived from Thy neg cells expressed hemoglobin, by day 11 less than 5% were hemoglobinized. In contrast, greater than 70% of the Thy low subset contained hemoglobinized cells at the end of the observation period. A similar transient appearance of myeloid progeny was also observed in colonies derived from c‐kit low Thy neg lymphoid progenitor cells. We conclude that these studies demonstrate commitment to the lymphoid lineage at the Thy low ‐to‐Thy neg interface, and that the loss of erythroid and myeloid potential is gradual rather than abrupt. Hemoglobinized colonies may be undergoing apoptosis because of down‐regulation of GATA‐1 or because of a death signal from surrounding nonerythrocytic cells.