Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Blood |
| Vol/bind | 105 |
| Udgave nummer | 4 |
| Sider (fra-til) | 1785-96 |
| Antal sider | 11 |
| ISSN | 0006-4971 |
| DOI | |
| Status | Udgivet - 2004 |
| Udgivet eksternt | Ja |
Bibliografisk note
Keywords: Apoptosis; Blotting, Western; Bone Marrow Cells; Cell Cycle Proteins; Cell Differentiation; Cell Separation; Cytoplasmic Granules; Gene Expression Profiling; Granulocyte Precursor Cells; Granulocytes; Humans; Ligands; Neutrophils; Oligonucleotide Array Sequence Analysis; Receptors, Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; Transcription, GeneticAdgang til dokumentet
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The transcriptional program of terminal granulocytic differentiation. / Theilgaard-Mönch, Kim; Jacobsen, Lars Christian; Borup, Rehannah; Rasmussen, Thomas; Bjerregaard, Malene Digmann; Nielsen, Finn Cilius; Cowland, Jack Bernard; Borregaard, Niels.
I: Blood, Bind 105, Nr. 4, 2004, s. 1785-96.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - The transcriptional program of terminal granulocytic differentiation.
AU - Theilgaard-Mönch, Kim
AU - Jacobsen, Lars Christian
AU - Borup, Rehannah
AU - Rasmussen, Thomas
AU - Bjerregaard, Malene Digmann
AU - Nielsen, Finn Cilius
AU - Cowland, Jack Bernard
AU - Borregaard, Niels
N1 - Keywords: Apoptosis; Blotting, Western; Bone Marrow Cells; Cell Cycle Proteins; Cell Differentiation; Cell Separation; Cytoplasmic Granules; Gene Expression Profiling; Granulocyte Precursor Cells; Granulocytes; Humans; Ligands; Neutrophils; Oligonucleotide Array Sequence Analysis; Receptors, Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic
PY - 2004
Y1 - 2004
N2 - To characterize the transcriptional program that governs terminal granulocytic differentiation in vivo, we performed comprehensive microarray analyses of human bone marrow populations highly enriched in promyelocytes (PMs), myelocytes/metamyelocytes (MYs), and neutrophils (bm-PMNs). These analyses identified 11 310 genes involved in differentiation, of which 6700 were differentially regulated, including previously unidentified effector proteins and surface receptors of neutrophils. Differentiation of PMs toward MYs was accompanied by a marked decline of proliferative and general cellular activity as defined by down-regulation of E2 promoter binding factor (E2F) target genes; cyclin dependent kinases 2, 4, and 6; and various metabolic, proteasomal, and mitochondrial genes. Expression patterns of apoptosis genes indicated death control by the p53 pathway in PMs and by death receptor pathways in bm-PMNs. Effector proteins critical for host defense were expressed successively throughout granulocytic differentiation, whereas receptors and receptor ligands essential for the activation of the host defense program were terminally up-regulated in bm-PMNs. The up-regulation of ligand-receptor pairs, which are defined inducers as well as target genes of nuclear factor-kappa B (NF-kappa B), suggests a constitutive activation of NF-kappa B in bm-PMNs by autocrine loops. Overall, these results define a granulocytic differentiation model governed by a highly coordinated fail-safe program, which promotes completion of differentiation before cells gain responsiveness toward activating stimuli that accompany infections.
AB - To characterize the transcriptional program that governs terminal granulocytic differentiation in vivo, we performed comprehensive microarray analyses of human bone marrow populations highly enriched in promyelocytes (PMs), myelocytes/metamyelocytes (MYs), and neutrophils (bm-PMNs). These analyses identified 11 310 genes involved in differentiation, of which 6700 were differentially regulated, including previously unidentified effector proteins and surface receptors of neutrophils. Differentiation of PMs toward MYs was accompanied by a marked decline of proliferative and general cellular activity as defined by down-regulation of E2 promoter binding factor (E2F) target genes; cyclin dependent kinases 2, 4, and 6; and various metabolic, proteasomal, and mitochondrial genes. Expression patterns of apoptosis genes indicated death control by the p53 pathway in PMs and by death receptor pathways in bm-PMNs. Effector proteins critical for host defense were expressed successively throughout granulocytic differentiation, whereas receptors and receptor ligands essential for the activation of the host defense program were terminally up-regulated in bm-PMNs. The up-regulation of ligand-receptor pairs, which are defined inducers as well as target genes of nuclear factor-kappa B (NF-kappa B), suggests a constitutive activation of NF-kappa B in bm-PMNs by autocrine loops. Overall, these results define a granulocytic differentiation model governed by a highly coordinated fail-safe program, which promotes completion of differentiation before cells gain responsiveness toward activating stimuli that accompany infections.
U2 - 10.1182/blood-2004-08-3346
DO - 10.1182/blood-2004-08-3346
M3 - Journal article
C2 - 15514007
VL - 105
SP - 1785
EP - 1796
JO - Blood
JF - Blood
SN - 0006-4971
IS - 4
ER -