TY - JOUR
T1 - C/EBPΑ is required for development of dendritic cell progenitors
AU - Welner, Robert S.
AU - Bararia, Deepak
AU - Amabile, Giovanni
AU - Czibere, Akos
AU - Benoukraf, Touati
AU - Bach, Christian
AU - Wansa, K. Disnika Senali Abayratna
AU - Ye, Min
AU - Zhang, Hong
AU - Iino, Tadafumi
AU - Hetherington, Christopher J.
AU - Akashi, Koichi
AU - Tenen, Daniel G.
N1 - Funding Information:
This work was supported by the American Italian Cancer Foundation (G.A.), the National Institutes of Health (grants HL56745 and DK080665 [D.G.T.], and HL56745, CA41456, CA66996, CA118316, and DK080665), the José Carreras Leukemia Foundation (FIJC F11/01) (R.S.W.), the German Research Foundation (DFG fellowship BA 4186/1-1) (C.B.) and the Singapore Ministry of Health’s National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award (D.G.T.).
Funding Information:
The authors thank all members of the Tenen Laboratory for helpful discussions, Junyan Zhang for her help with mice, and the BIDMC flow cytometry facility for their expertise. This work was supported by the American Italian Cancer Foundation (G.A.), the National Institutes of Health (grants HL56745 and DK080665 [D.G.T.], and HL56745, CA41456, CA66996, CA118316, and DK080665), the Jos? Carreras Leukemia Foundation (FIJC F11/01) (R.S.W.), the German Research Foundation (DFG fellowship BA 4186/1-1) (C.B.) and the Singapore Ministry of Health?s National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award (D.G.T.).
Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013/5/16
Y1 - 2013/5/16
N2 - Dendritic cells (DCs) are master regulators of the immune system, but molecular regulation of early DC differentiation has been poorly understood. Here, we report that the transcription factor C/EBPa coordinates the development of progenitor cells required for production of multiple categories of DCs. C/EBPa was needed for differentiation from stem/progenitor cells to common DC progenitors (CDPs), but not for transition of CDP to mature DCs. C/EBPa deletion in mature DCs did not affect their numbers or function, suggesting that this transcription factor is not needed for maintenance of DCs in lymphoid tissues. ChIP-seq and microarrays were used to identify candidate genes regulated by C/EBPa and required for DC formation. Genes previously shown to be critical for DC formation were bound by C/EBPa, and their expression was decreased in the earliest hematopoietic compartments in the absence of C/EBPa. These data indicate that C/EBPa is important for the earliest stages of steady-state DC differentiation.
AB - Dendritic cells (DCs) are master regulators of the immune system, but molecular regulation of early DC differentiation has been poorly understood. Here, we report that the transcription factor C/EBPa coordinates the development of progenitor cells required for production of multiple categories of DCs. C/EBPa was needed for differentiation from stem/progenitor cells to common DC progenitors (CDPs), but not for transition of CDP to mature DCs. C/EBPa deletion in mature DCs did not affect their numbers or function, suggesting that this transcription factor is not needed for maintenance of DCs in lymphoid tissues. ChIP-seq and microarrays were used to identify candidate genes regulated by C/EBPa and required for DC formation. Genes previously shown to be critical for DC formation were bound by C/EBPa, and their expression was decreased in the earliest hematopoietic compartments in the absence of C/EBPa. These data indicate that C/EBPa is important for the earliest stages of steady-state DC differentiation.
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U2 - 10.1182/blood-2012-10-463448
DO - 10.1182/blood-2012-10-463448
M3 - Article
C2 - 23547051
AN - SCOPUS:84880987215
VL - 121
SP - 4073
EP - 4081
JO - Blood
JF - Blood
SN - 0006-4971
IS - 20
ER -