The transcriptional program of terminal granulocytic differentiation

  • Theilgaard-Mönch K
  • Jacobsen L
  • Borup R
 et al. 
  • 104


    Mendeley users who have this article in their library.
  • 175


    Citations of this article.


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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text


  • Kim Theilgaard-Mönch

  • Lars Christian Jacobsen

  • Rehannah Borup

  • Thomas Rasmussen

  • Malene Digmann Bjerregaard

  • Finn Cilius Nielsen

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free