TY - JOUR
T1 - Developmental Regulated Cell Death Programs Account for Colony Elimination and Unstable Mixed-Chimerism in B. Schlosseri: Implications for Allogeneic Graft Survival
AU - Corey, Daniel M.
AU - Kowarsky, Mark
AU - Rosental, Benyamin
AU - Ishizuka, Katherine
AU - Palmeri, Karla
AU - Sinha, Rahul
AU - Voskoboynik, Ayelet
AU - Quake, Stephen
AU - Weissman, Irving
PY - 2016/3
Y1 - 2016/3
N2 - To understand mechanisms fundamental to the maintenance
of allogeneic mixed-chimerism we conducted a detailed
anatomic and transcriptional analysis of B. schlosseri natural
chimeras, a colonial protochordate that undergoes a genetically controlled natural transplantation reaction to create
natural parabionts. The life history of B. schlosseri offers a
unique platform to study persistence of allogeneic cells in a
host. Fusion of blood vessels between two histocompatible,
but genetically distinct organisms or colonies creates natural
chimeras. Natural history studies among fused-colonies show
partners rarely exist as stable chimeras. One chimeric partner
is often eliminated in a process of allogeneic resorption. Here
we show elimination of chimeric partners involves co-opting
programmed cell death and cell-removal pathways during
the developmental-regulated ‘takeover’ period of colony life.
B. schlosseri colonies reproduce by a process of asexual
budding in a highly coordinated weekly blastogenic cycle that
ends in a massive apoptotic and phagocytic event of parental
individuals. We identified 4266 genes from global RNA-seq
expression profiling that changed at least four-fold (FDR <
0.05) shared by both blastogenic takeover and chimeric
fusion-partner resorption. Among these, 275 genes increased
by expression of at least 50 fold. These include an IL-17 family
member (IL-17C), the phagocytic receptors (MerTK, AXL), a
programmed cell removal factor (MFGE-8), vascular adhesion
molecules (SELP, SELE, Tie1), complement factors (C3, MASP1,
MASP2), coagulation factors (F2, F8, KLK3, KLKB1), TNF associated proteins (TRAF3, TRAF4), and matrix metalloproteinases (MMP9, MMP14, MMP16). Among the major
pathways identified in chimeric partner elimination are key
innate immune signaling processes under the GO terms for
“blood coagulation”, “cell death”, “proteolysis,” and “cellular
adhesion.” Major characteristics of the transcriptional and
cellular programs that underlie chimeric fusion-partner
resorption and their implications for development of new
strategies to promote allogeneic graft survival in hematopoietic cell transplantation [HCT] will be presented.
AB - To understand mechanisms fundamental to the maintenance
of allogeneic mixed-chimerism we conducted a detailed
anatomic and transcriptional analysis of B. schlosseri natural
chimeras, a colonial protochordate that undergoes a genetically controlled natural transplantation reaction to create
natural parabionts. The life history of B. schlosseri offers a
unique platform to study persistence of allogeneic cells in a
host. Fusion of blood vessels between two histocompatible,
but genetically distinct organisms or colonies creates natural
chimeras. Natural history studies among fused-colonies show
partners rarely exist as stable chimeras. One chimeric partner
is often eliminated in a process of allogeneic resorption. Here
we show elimination of chimeric partners involves co-opting
programmed cell death and cell-removal pathways during
the developmental-regulated ‘takeover’ period of colony life.
B. schlosseri colonies reproduce by a process of asexual
budding in a highly coordinated weekly blastogenic cycle that
ends in a massive apoptotic and phagocytic event of parental
individuals. We identified 4266 genes from global RNA-seq
expression profiling that changed at least four-fold (FDR <
0.05) shared by both blastogenic takeover and chimeric
fusion-partner resorption. Among these, 275 genes increased
by expression of at least 50 fold. These include an IL-17 family
member (IL-17C), the phagocytic receptors (MerTK, AXL), a
programmed cell removal factor (MFGE-8), vascular adhesion
molecules (SELP, SELE, Tie1), complement factors (C3, MASP1,
MASP2), coagulation factors (F2, F8, KLK3, KLKB1), TNF associated proteins (TRAF3, TRAF4), and matrix metalloproteinases (MMP9, MMP14, MMP16). Among the major
pathways identified in chimeric partner elimination are key
innate immune signaling processes under the GO terms for
“blood coagulation”, “cell death”, “proteolysis,” and “cellular
adhesion.” Major characteristics of the transcriptional and
cellular programs that underlie chimeric fusion-partner
resorption and their implications for development of new
strategies to promote allogeneic graft survival in hematopoietic cell transplantation [HCT] will be presented.
U2 - 10.1016/j.bbmt.2015.11.780
DO - 10.1016/j.bbmt.2015.11.780
M3 - תקציר הצגה בכנס
SN - 1083-8791
VL - 22
SP - S310-S310
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 3
ER -