The ETS family transcription factor PU.1 is necessary for the maintenance of fetal liver hematopoietic stem cells.
PU.1 is a member of the ETS family of transcription factors and is required for the development of multiple hematopoietic lineages. PU.1(-/-) mice die from hematopoietic failure at about embryonic day 18.5 (e18.5) and show a complete absence of B cells, mature T cells, and macrophages. This phenotype suggests that PU.1 may function at the level of the hematopoietic stem cell (HSC) or a multilineage progenitor. To investigate the role of PU.1 in the regulation of HSCs, PU.1(-/-) embryos were analyzed at various stages of embryonic development. The absolute number and frequency of HSCs were determined by flow cytometric analysis of c-Kit(+)Thy-1.1(lo)Lin(-)Sca-1(+) (KTLS) cells. We found that KTLS cells were absent or severely reduced in PU.1(-/-) fetal liver from e12.5 to e15.5. Progenitor cells with a c-Kit(+)Lin(-)AA4.1(+) and c-Kit(+)Lin(-)CD34(+) phenotype were also severely reduced. In addition, PU.1(-/-) fetal liver at e14.5 lacked common myeloid progenitors (CMPs) and granulocyte-macrophage progenitors (GMPs) but retained megakaryocyteerythroid progenitors (MEPs). Consistent with the loss of HSC activity, a 10-fold reduction in erythroid progenitors (mature erythroid burst-forming units [BFUEs]) was observed between e14.5 and e16.5. These data suggest that PU.1 plays an important role in the maintenance or expansion of HSC number in murine fetal liver.
Kim
Hyung-Gyoon
HG
Department of Microbiology and Division of Developmental and Clinical Immunology, The University of Alabama at Birmingham, WTI Room 387, 1824 Sixth Ave South, Birmingham AL 35294-3300, USA.
de Guzman
Cristina G
CG
Swindle
C Scott
CS
Cotta
Claudiu V
CV
Gartland
Larry
L
Scott
Edward W
EW
Klug
Christopher A
CA
D000818:Animals; D003433:Crosses, Genetic; D005333:Fetus; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000099232:Proto-Oncogene Protein Spi-1
D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1