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p62 Is Required for Stem Cell/Progenitor Retention through Inhibition of IKK/NF-kB/Ccl4 Signaling at the Bone Marrow Macrophage-Osteoblast Niche

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Title p62 Is Required for Stem Cell/Progenitor Retention through Inhibition of IKK/NF-kB/Ccl4 Signaling at the Bone Marrow Macrophage-Osteoblast Niche
 
Creator Chang, Kyung Hee
Sengupta, Amitava
Nayak, Ramesh C
Duran, Angeles
Lee, Sang Jun
Pratt, Ronald G
Wellendorf, Ashley M
Hill, Sarah E
Watkins, Marcus
Gonzalez-Nieto, Daniel
Aronow, Bruce J
Starczynowski, Daniel T
Civitelli, Roberto
Diaz-Meco, Maria T
Moscat, Jorge
Cancelas, Jose A
 
Subject Cancer Biology and Inflammatory Disorder Division
 
Description In the bone marrow (BM), hematopoietic progenitors
(HPs) reside in specific anatomical niches near osteoblasts
(Obs), macrophages (MFs), and other cells forming the BM microenvironment. A connection between immunosurveillance and traffic of HP has been demonstrated, but the regulatory signals that instruct the immune regulation of HP circulation are unknown. We discovered that the BM microenvironment deficiency of p62, an autophagy regulator and signal organizer, results in loss of autophagic repression of macrophage contact-dependent activation of
Ob NF-kB signaling. Consequently, Ob p62-deficient
mice lose bone, Ob Ccl4 expression, and HP chemotaxis
toward Cxcl12, resulting in egress of short-term
hematopoietic stem cells and myeloid progenitors.
Finally, Ccl4 expression and myeloid progenitor
egress are reversed by deficiency of the p62 PB1-
binding partner Nbr1. A functional ‘‘MF-Ob niche’’
is required for myeloid progenitor/short-term stem
cell retention, in which Ob p62 is required to maintain
NF-kB signaling repression, osteogenesis, and BM
progenitor retention.
 
Date 2014
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2140/1/CELL_REPORTS__9_(_6)2084%2D2097_;2014.pdf
Chang, Kyung Hee and Sengupta, Amitava and Nayak, Ramesh C and Duran, Angeles and Lee, Sang Jun and Pratt, Ronald G and Wellendorf, Ashley M and Hill, Sarah E and Watkins, Marcus and Gonzalez-Nieto, Daniel and Aronow, Bruce J and Starczynowski, Daniel T and Civitelli, Roberto and Diaz-Meco, Maria T and Moscat, Jorge and Cancelas, Jose A (2014) p62 Is Required for Stem Cell/Progenitor Retention through Inhibition of IKK/NF-kB/Ccl4 Signaling at the Bone Marrow Macrophage-Osteoblast Niche. Cell Reports, 9 (6). pp. 2084-2097.
 
Relation http://dx.doi.org/10.1016/j.celrep.2014.11.031
http://www.eprints.iicb.res.in/2140/