Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation

Mi Cai, Ellen M. Langer, Jennifer G. Gill, Ansuman T. Satpathy, Jörn C. Albring, Wumesh Kc, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Myeloid ecotropic viral integration site 1 (Meis1) forms a heterodimer with Pbx1 that augments Hox-dependent gene expression and is associated with leukemogenesis and HSC self-renewal. Here we identified 2 independent actions of Meis1 in hematopoietic development: one regulating cellular proliferation and the other involved in megakaryocyte lineage development. First, we found that endogenous Mesp1 indirectly induces Meis1 and Meis2 in endothelial cells derived from embryonic stem cells. Overexpression of Meis1 and Meis2 greatly enhanced the formation of hematopoietic colonies from embryonic stem cells, with the exception of erythroid colonies, by maintaining hematopoietic progenitor cells in a state of proliferation. Second, overexpression of Meis1 repressed the development of early erythroid progenitors, acting in vivo at the megakaryocyte-erythroid progenitor stage to skew development away from erythroid generation and toward megakaryocyte development. This previously unrecognized action of Meis1 may explain the embryonic lethality observed in Meis1 -/- mice that arises from failure of lymphatic-venous separation and can result as a consequence of defective platelet generation. These results show that Meis1 exerts 2 independent functions, with its role in proliferation of hematopoietic progenitors acting earlier in development from its influence on the fate choice at the megakaryocyte-erythroid progenitor between megakaryocytic and erythroid development.

Original languageEnglish (US)
Pages (from-to)335-346
Number of pages12
JournalBlood
Volume120
Issue number2
DOIs
StatePublished - Jul 12 2012

Fingerprint

Virus Integration
Cell proliferation
Cell Proliferation
Megakaryocyte-Erythroid Progenitor Cells
Megakaryocytes
Embryonic Stem Cells
Stem cells
Homeobox Genes
Endothelial cells
Hematopoietic Stem Cells
Platelets
Gene expression
Blood Platelets
Endothelial Cells
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation. / Cai, Mi; Langer, Ellen M.; Gill, Jennifer G.; Satpathy, Ansuman T.; Albring, Jörn C.; Kc, Wumesh; Murphy, Theresa L.; Murphy, Kenneth M.

In: Blood, Vol. 120, No. 2, 12.07.2012, p. 335-346.

Research output: Contribution to journalArticle

Cai, M, Langer, EM, Gill, JG, Satpathy, AT, Albring, JC, Kc, W, Murphy, TL & Murphy, KM 2012, 'Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation', Blood, vol. 120, no. 2, pp. 335-346. https://doi.org/10.1182/blood-2012-01-403139
Cai, Mi ; Langer, Ellen M. ; Gill, Jennifer G. ; Satpathy, Ansuman T. ; Albring, Jörn C. ; Kc, Wumesh ; Murphy, Theresa L. ; Murphy, Kenneth M. / Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation. In: Blood. 2012 ; Vol. 120, No. 2. pp. 335-346.
@article{a71ccb77b3da45dda763e958d9de7fde,
title = "Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation",
abstract = "Myeloid ecotropic viral integration site 1 (Meis1) forms a heterodimer with Pbx1 that augments Hox-dependent gene expression and is associated with leukemogenesis and HSC self-renewal. Here we identified 2 independent actions of Meis1 in hematopoietic development: one regulating cellular proliferation and the other involved in megakaryocyte lineage development. First, we found that endogenous Mesp1 indirectly induces Meis1 and Meis2 in endothelial cells derived from embryonic stem cells. Overexpression of Meis1 and Meis2 greatly enhanced the formation of hematopoietic colonies from embryonic stem cells, with the exception of erythroid colonies, by maintaining hematopoietic progenitor cells in a state of proliferation. Second, overexpression of Meis1 repressed the development of early erythroid progenitors, acting in vivo at the megakaryocyte-erythroid progenitor stage to skew development away from erythroid generation and toward megakaryocyte development. This previously unrecognized action of Meis1 may explain the embryonic lethality observed in Meis1 -/- mice that arises from failure of lymphatic-venous separation and can result as a consequence of defective platelet generation. These results show that Meis1 exerts 2 independent functions, with its role in proliferation of hematopoietic progenitors acting earlier in development from its influence on the fate choice at the megakaryocyte-erythroid progenitor between megakaryocytic and erythroid development.",
author = "Mi Cai and Langer, {Ellen M.} and Gill, {Jennifer G.} and Satpathy, {Ansuman T.} and Albring, {J{\"o}rn C.} and Wumesh Kc and Murphy, {Theresa L.} and Murphy, {Kenneth M.}",
year = "2012",
month = "7",
day = "12",
doi = "10.1182/blood-2012-01-403139",
language = "English (US)",
volume = "120",
pages = "335--346",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - Dual actions of Meis1 inhibit erythroid progenitor development and sustain general hematopoietic cell proliferation

AU - Cai, Mi

AU - Langer, Ellen M.

AU - Gill, Jennifer G.

AU - Satpathy, Ansuman T.

AU - Albring, Jörn C.

AU - Kc, Wumesh

AU - Murphy, Theresa L.

AU - Murphy, Kenneth M.

PY - 2012/7/12

Y1 - 2012/7/12

N2 - Myeloid ecotropic viral integration site 1 (Meis1) forms a heterodimer with Pbx1 that augments Hox-dependent gene expression and is associated with leukemogenesis and HSC self-renewal. Here we identified 2 independent actions of Meis1 in hematopoietic development: one regulating cellular proliferation and the other involved in megakaryocyte lineage development. First, we found that endogenous Mesp1 indirectly induces Meis1 and Meis2 in endothelial cells derived from embryonic stem cells. Overexpression of Meis1 and Meis2 greatly enhanced the formation of hematopoietic colonies from embryonic stem cells, with the exception of erythroid colonies, by maintaining hematopoietic progenitor cells in a state of proliferation. Second, overexpression of Meis1 repressed the development of early erythroid progenitors, acting in vivo at the megakaryocyte-erythroid progenitor stage to skew development away from erythroid generation and toward megakaryocyte development. This previously unrecognized action of Meis1 may explain the embryonic lethality observed in Meis1 -/- mice that arises from failure of lymphatic-venous separation and can result as a consequence of defective platelet generation. These results show that Meis1 exerts 2 independent functions, with its role in proliferation of hematopoietic progenitors acting earlier in development from its influence on the fate choice at the megakaryocyte-erythroid progenitor between megakaryocytic and erythroid development.

AB - Myeloid ecotropic viral integration site 1 (Meis1) forms a heterodimer with Pbx1 that augments Hox-dependent gene expression and is associated with leukemogenesis and HSC self-renewal. Here we identified 2 independent actions of Meis1 in hematopoietic development: one regulating cellular proliferation and the other involved in megakaryocyte lineage development. First, we found that endogenous Mesp1 indirectly induces Meis1 and Meis2 in endothelial cells derived from embryonic stem cells. Overexpression of Meis1 and Meis2 greatly enhanced the formation of hematopoietic colonies from embryonic stem cells, with the exception of erythroid colonies, by maintaining hematopoietic progenitor cells in a state of proliferation. Second, overexpression of Meis1 repressed the development of early erythroid progenitors, acting in vivo at the megakaryocyte-erythroid progenitor stage to skew development away from erythroid generation and toward megakaryocyte development. This previously unrecognized action of Meis1 may explain the embryonic lethality observed in Meis1 -/- mice that arises from failure of lymphatic-venous separation and can result as a consequence of defective platelet generation. These results show that Meis1 exerts 2 independent functions, with its role in proliferation of hematopoietic progenitors acting earlier in development from its influence on the fate choice at the megakaryocyte-erythroid progenitor between megakaryocytic and erythroid development.

UR - http://www.scopus.com/inward/record.url?scp=84864072058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864072058&partnerID=8YFLogxK

U2 - 10.1182/blood-2012-01-403139

DO - 10.1182/blood-2012-01-403139

M3 - Article

VL - 120

SP - 335

EP - 346

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -