Imaging hematopoietic precursor division in real time.
Stem cells are thought to balance self-renewal and differentiation through asymmetric and symmetric divisions, but whether such divisions occur during hematopoietic development remains unknown. Using a Notch reporter mouse, in which GFP acts as a sensor for differentiation, we image hematopoietic precursors and show that they undergo both symmetric and asymmetric divisions. In addition we show that the balance between these divisions is not hardwired but responsive to extrinsic and intrinsic cues. Precursors in a prodifferentiation environment preferentially divide asymmetrically, whereas those in a prorenewal environment primarily divide symmetrically. Oncoproteins can also influence division pattern: although BCR-ABL predominantly alters the rate of division and death, NUP98-HOXA9 promotes symmetric division, suggesting that distinct oncogenes subvert different aspects of cellular function. These studies establish a system for tracking division of hematopoietic precursors and show that the balance of symmetric and asymmetric division can be influenced by the microenvironment and subverted by oncogenes.
Wu
Mingfu
M
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Kwon
Hyog Young
HY
Rattis
Frederique
F
Blum
Jordan
J
Zhao
Chen
C
Ashkenazi
Rina
R
Jackson
Trachette L
TL
Gaiano
Nicholas
N
Oliver
Tim
T
Reya
Tannishtha
T
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D009419:Nerve Tissue Proteins / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D010641:Phenotype; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D013997:Time Factors
D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; C106293:Numb protein, mouse; D051880:Receptors, Notch; C485184:enhanced green fluorescent protein; C097899:homeobox protein HOXA9; C093350:nuclear pore complex protein 98; D049452:Green Fluorescent Proteins; D016044:Fusion Proteins, bcr-abl