title: Erg is required for self-renewal of hematopoietic stem cells during stress hematopoiesis in mice.
abstract: Hematopoietic stem cells (HSCs) are rare residents of the bone marrow responsible for the lifelong production of blood cells. Regulation of the balance between HSC self-renewal and differentiation is central to hematopoiesis, allowing precisely regulated generation of mature blood cells at steady state and expanded production at times of rapid need, as well as maintaining ongoing stem cell capacity. Erg, a member of the Ets family of transcription factors, is deregulated in cancers; and although Erg is known to be required for regulation of adult HSCs, its precise role has not been defined. We show here that, although heterozygosity for functional Erg is sufficient for adequate steady-state HSC maintenance, Erg(+/Mld2) mutant mice exhibit impaired HSC self-renewal after bone marrow transplantation or during recovery from myelotoxic stress. Moreover, although mice functionally compromised for either Erg or Mpl, the receptor for thrombopoietin, a key regulator of HSC quiescence, maintained sufficient HSC activity to sustain hematopoiesis, Mpl(-/-) Erg(+/Mld2) compound mutant mice displayed exacerbated stem cell deficiencies and bone marrow failure. Thus, Erg is a critical regulator of adult HSCs, essential for maintaining self-renewal at times of high HSC cycling.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: Ashley P
authors.initials: AP
authors.lastname: Ng
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Loughran
authors.forename: Donald
authors.initials: D
authors.lastname: Metcalf
authors.forename: Craig D
authors.initials: CD
authors.lastname: Hyland
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: de Graaf
authors.forename: Yifang
authors.initials: Y
authors.lastname: Hu
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Smyth
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Hilton
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Kile
authors.forename: Warren S
authors.initials: WS
authors.lastname: Alexander
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002455:Cell Division; D003114:Colony-Forming Units Assay; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D020125:Mutation, Missense; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D011828:Radiation Chimera; D053628:Receptors, Thrombopoietin / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG
chemical_list: C531115:ERG protein, mouse; C481270:Mpl protein, mouse; D015513:Oncogene Proteins; D053628:Receptors, Thrombopoietin; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG