PMID- 22062221
OWN - NLM
STAT- MEDLINE
DCOM- 20120217
LR  - 20121115
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 180
IP  - 1
DP  - 2012 Jan
TI  - Notch-induced hIL-6 production facilitates the maintenance of self-renewal of 
      hCD34+ cord blood cells through the activation of Jak-PI3K-STAT3 pathway.
PG  - 351-64
LID - 10.1016/j.ajpath.2011.09.030 [doi]
AB  - Ex vivo expansion of CD34(+) stem cells in contact culture between 
      hCD34(+)CD38(-)Lin(-) cord blood stem cells and human delta-like-expressing 
      AFT024 feeder cells revealed increased amounts of stemness-related proteins such 
      as HoxB4, GATA2, Bmi-1, and p21 and anti-apoptotic proteins such as Bcl-2, 
      Bcl-xL, Mcl-1, and phospho-Bad, when compared with control or noncontact culture. 
      Production of human IL-6 (hIL-6) was markedly elevated in the culture, but was 
      profoundly inhibited by treatment with gamma-secretase inhibitor. In addition, 
      Notch-induced activation of STAT3 was directly involved in gene expression of 
      hIL-6 and soluble hIL-6Ralpha, indicating the close linkage between Notch signaling 
      and hIL-6 production. Furthermore, depletion of soluble hIL-6 (with 
      hIL-6-specific antibodies) and inhibition of IL-6-mediated signals (with a Jak1 
      inhibitor and wortmannin) severely affected the maintenance of self-renewal of 
      hCD34(+) cord blood cells. It was also observed that the ex vivo expanded CD34(+) 
      cord blood cells were induced to reconstitute human immune cells in nonobese 
      diabetic mice with severe combined immunodeficiency when compared with freshly 
      isolated CD34(+) cord blood cells. Together, these results strongly demonstrate 
      that Notch signaling in the "cell-to-cell contact" between hCD34(+) cord blood 
      and delta-like-expressing AFT024 feeder cells facilitates maintenance of 
      self-renewal of hCD34(+) cord blood cells through direct regulation of hIL-6 
      production.
CI  - Copyright (c) 2012 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Choi, Bongkum
AU  - Choi B
AD  - Department of Molecular Medicine, Samsung Medical Center, Sungkyunkwan University 
      School of Medicine, Seoul, South Korea.
FAU - Chun, Eunyoung
AU  - Chun E
FAU - Kim, So Yong
AU  - Kim SY
FAU - Kim, Miyoung
AU  - Kim M
FAU - Lee, Ki-Young
AU  - Lee KY
FAU - Kim, Sung Joo
AU  - Kim SJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111107
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Antigens, CD34)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Notch)
RN  - 0 (STAT3 Transcription Factor)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.2 (Janus Kinase 1)
SB  - IM
MH  - Animals
MH  - Antigens, CD34/*metabolism
MH  - Blood Cells/*immunology
MH  - Cell Proliferation
MH  - Fetal Blood/*cytology
MH  - Humans
MH  - Interleukin-6/*biosynthesis
MH  - Janus Kinase 1/antagonists & inhibitors/metabolism
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Receptors, Notch/*physiology
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/physiology
MH  - Stem Cells/physiology
EDAT- 2011/11/09 06:00
MHDA- 2012/02/18 06:00
CRDT- 2011/11/09 06:00
PHST- 2011/04/19 00:00 [received]
PHST- 2011/09/04 00:00 [revised]
PHST- 2011/09/12 00:00 [accepted]
PHST- 2011/11/09 06:00 [entrez]
PHST- 2011/11/09 06:00 [pubmed]
PHST- 2012/02/18 06:00 [medline]
AID - S0002-9440(11)00922-9 [pii]
AID - 10.1016/j.ajpath.2011.09.030 [doi]
PST - ppublish
SO  - Am J Pathol. 2012 Jan;180(1):351-64. doi: 10.1016/j.ajpath.2011.09.030. Epub 2011 
      Nov 7.