Downregulation of Mpl marks the transition to lymphoid-primed multipotent progenitors with gradual loss of granulocyte-monocyte potential.

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Downregulation of Mpl marks the transition to lymphoid-primed multipotent progenitors with gradual loss of granulocyte-monocyte potential. / Luc, Sidinh; Anderson, Kristina; Kharazi, Shabnam; Buza-Vidas, Natalija; Böiers, Charlotta; Jensen, Christina; Ma, Zhi; Wittmann, Lilian; Jacobsen, Sten Eirik W.

In: Blood, Vol. 111, No. 7, 2008, p. 3424-3434.

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Luc, Sidinh ; Anderson, Kristina ; Kharazi, Shabnam ; Buza-Vidas, Natalija ; Böiers, Charlotta ; Jensen, Christina ; Ma, Zhi ; Wittmann, Lilian ; Jacobsen, Sten Eirik W. / Downregulation of Mpl marks the transition to lymphoid-primed multipotent progenitors with gradual loss of granulocyte-monocyte potential. In: Blood. 2008 ; Vol. 111, No. 7. pp. 3424-3434.

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TY - JOUR

T1 - Downregulation of Mpl marks the transition to lymphoid-primed multipotent progenitors with gradual loss of granulocyte-monocyte potential.

AU - Luc, Sidinh

AU - Anderson, Kristina

AU - Kharazi, Shabnam

AU - Buza-Vidas, Natalija

AU - Böiers, Charlotta

AU - Jensen, Christina

AU - Ma, Zhi

AU - Wittmann, Lilian

AU - Jacobsen, Sten Eirik W

PY - 2008

Y1 - 2008

N2 - Evidence for a novel route of adult hematopoietic stem cell lineage commitment through Lin(-)Sca-1(+)Kit(+)Flt3(hi) (LSKFlt3(hi)) lymphoid-primed multipotent progenitors (LMPPs) with granulocyte/monocyte (GM) and lymphoid but little or no megakaryocyte/erythroid (MkE) potential was recently challenged, as LSKFlt3(hi) cells were reported to possess MkE potential. Herein residual (1-2%) MkE potential segregated almost entirely with LSKFlt3(hi) cells expressing the thrombopoietin receptor (Mpl), whereas LSKFlt3(hi)Mpl(-) LMPPs lacked significant MkE potential in vitro and in vivo, but sustained combined GM and lymphoid potentials, and co-expressed GM and lymphoid but not MkE transcriptional lineage programs. Gradually increased transcriptional lymphoid priming in single LMPPs from Rag1(GFP) mice was shown to occur in the presence of maintained GM lineage priming, but gradually reduced GM lineage potential. These functional and molecular findings reinforce the existence of GM/lymphoid restricted progenitors with dramatically downregulated probability for committing towards MkE fates, and support that lineage restriction occurs through gradual rather than abrupt changes in specific lineage potentials.

AB - Evidence for a novel route of adult hematopoietic stem cell lineage commitment through Lin(-)Sca-1(+)Kit(+)Flt3(hi) (LSKFlt3(hi)) lymphoid-primed multipotent progenitors (LMPPs) with granulocyte/monocyte (GM) and lymphoid but little or no megakaryocyte/erythroid (MkE) potential was recently challenged, as LSKFlt3(hi) cells were reported to possess MkE potential. Herein residual (1-2%) MkE potential segregated almost entirely with LSKFlt3(hi) cells expressing the thrombopoietin receptor (Mpl), whereas LSKFlt3(hi)Mpl(-) LMPPs lacked significant MkE potential in vitro and in vivo, but sustained combined GM and lymphoid potentials, and co-expressed GM and lymphoid but not MkE transcriptional lineage programs. Gradually increased transcriptional lymphoid priming in single LMPPs from Rag1(GFP) mice was shown to occur in the presence of maintained GM lineage priming, but gradually reduced GM lineage potential. These functional and molecular findings reinforce the existence of GM/lymphoid restricted progenitors with dramatically downregulated probability for committing towards MkE fates, and support that lineage restriction occurs through gradual rather than abrupt changes in specific lineage potentials.

U2 - 10.1182/blood-2007-08-108324

DO - 10.1182/blood-2007-08-108324

M3 - Article

VL - 111

SP - 3424

EP - 3434

JO - Blood

JF - Blood

SN - 1528-0020

IS - 7

ER -