Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment.
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.
Adolfsson
Jörgen
J
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology, Lund University, Sweden.
Månsson
Robert
R
Buza-Vidas
Natalija
N
Hultquist
Anne
A
Liuba
Karina
K
Jensen
Christina T
CT
Bryder
David
D
Yang
Liping
L
Borge
Ole-Johan
OJ
Thoren
Lina A M
LA
Anderson
Kristina
K
Sitnicka
Ewa
E
Sasaki
Yutaka
Y
Sigvardsson
Mikael
M
Jacobsen
Sten Eirik W
SE
D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000502:physiology*; D015536:Down-Regulation; D004912:Erythrocytes / Q000166:cytology; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000145:classification* / Q000166:cytology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3
D011518:Proto-Oncogene Proteins; C497971:Flt3 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3