The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12.
Gene targeting studies have shown that the transcription factor SCL is critically important for embryonic hematopoiesis, but the early lethality of SCL null mice has precluded the genetic analysis of its function in the adult. We have now generated a conditional knockout of SCL by using CreLox technology and an IFN-inducible Cre transgenic mouse. Deletion of SCL in adult mice perturbed megakaryopoiesis and erythropoiesis with the loss of early progenitor cells in both lineages. This led to a blunted response to the hematopoietic stress induced by polyinosinic-polycytidylic acid, with a persistently low platelet count and hematocrit compared with controls. In contrast, progenitors of granulocyte and macrophage lineages were not affected, even in the setting of stress. Immature progenitor cells (day 12 colony-forming unit spleen) with multilineage capacity were still present in the SCL null bone marrow, but these progenitors had lost the capacity to generate erythroid and megakaryocyte cells, and colonies were composed of only myeloid cells. These results suggest that SCL is critical for megakaryopoiesis and erythropoiesis, but is dispensable for production of myeloid cells during adult hematopoiesis.
Hall
Mark A
MA
Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia. hall@wehi.edu.au
Curtis
David J
DJ
Metcalf
Donald
D
Elefanty
Andrew G
AG
Sourris
K
K
Robb
Lorraine
L
Gothert
Joachim R
JR
Jane
Stephen M
SM
Begley
C Glenn
CG
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D051792:Basic Helix-Loop-Helix Proteins; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000166:cytology*; D005434:Flow Cytometry; D017353:Gene Deletion; D005822:Genetic Vectors; D006098:Granulocytes / Q000166:cytology; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D022423:Myeloid Cells / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000502:physiology*; D011990:Receptors, Transferrin; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D011990:Receptors, Transferrin; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C068126:CD71 antigen; C489366:Tal1 protein, mouse