Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential:: A revised road map for adult blood lineage commitment

被引：899

作者：

Adolfsson, J ^{[1
]}

Månsson, R ^{[1
]}

Buza-Vidas, N ^{[1
]}

Hultquist, A ^{[1
]}

Liuba, K ^{[1
]}

Jensen, CT ^{[1
]}

Bryder, D ^{[1
]}

Yang, LP ^{[1
]}

Borge, OJ ^{[1
]}

Thoren, LAM ^{[1
]}

Anderson, K ^{[1
]}

Sitnicka, E ^{[1
]}

Sasaki, Y ^{[1
]}

Sigvardsson, M ^{[1
]}

Jacobsen, SEW ^{[1
]}

机构：

[1] Lund Univ, Hematopoiet Stem Cell Lab, Lund Strateg Res Ctr Stem Cell Biol & Cell Therap, S-22184 Lund, Sweden

来源：

CELL | 2005年 / 121卷 / 02期

关键词：

D O I：

10.1016/j.cell.2005.02.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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(+)ckit(+)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-l(+)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.

引用

页码：295 / 306

页数：12

共 54 条

[1] Upregulation of flt3 expression within the bone marrow Lin-Sca1+c-kit+ stem cell compartment is accompanied by loss of self-renewal capacity [J].