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All blood cell lineages derive from a common hematopoietic stem cell (HSC). The current model implicates that the first lineage commitment step of adult pluripotent HSCs results in a strict separation into common lymphoid and common myeloid precursors. We present evidence for a population of cells which, although sustaining a high proliferative and combined lympho-myeloid differentiation potential, have lost the ability to adopt erythroid and megakaryocyte lineage fates. Cells in the Lin-Sca-1+c-kit+ HSC compartment coexpressing high levels of the tyrosine kinase receptor Flt3 sustain granulocyte, monocyte, and B and T cell potentials but in contrast to Lin-Sca-1+c-kit+Flt3- HSCs fail to produce significant erythroid and megakaryocytic progeny. This distinct lineage restriction site is accompanied by downregulation of genes for regulators of erythroid and megakaryocyte development. In agreement with representing a lymphoid primed progenitor, Lin-Sca-1+c-kit+CD34+Flt3+ cells display upregulated IL-7 receptor gene expression. Based on these observations, we propose a revised road map for adult blood lineage development.

Original publication

DOI

10.1016/j.cell.2005.02.013

Type

Journal article

Journal

Cell

Publication Date

22/04/2005

Volume

121

Pages

295 - 306

Keywords

Age Factors, Animals, Cell Differentiation, Cell Lineage, Down-Regulation, Erythrocytes, Gene Expression Regulation, In Vitro Techniques, Megakaryocytes, Mice, Mice, Inbred C57BL, Myeloid Progenitor Cells, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, fms-Like Tyrosine Kinase 3