TY - JOUR
T1 - The Drosophila BCL6 homolog ken and barbie promotes somatic stem cell self-renewal in the testis niche
AU - Issigonis, Melanie
AU - Matunis, Erika
N1 - Funding Information:
We thank members of the fly community for their generosity including Dr. Martin Zeidler for the ken k11035 and UAS-ken stocks; Dr. Doug Harrison for the UAS-hop TumL and hs-upd stocks; Dr. Allan Spradling for the c587-GAL4 stock; Dr. Mark Van Doren for the nanos-GAL4 stock; Dr. Jim Skeath for the ZFH1 antibody; Dr. Dorothea Godt for the Tj antibody; and Dr. Erika Bach for the Stat92E antibody. We also thank the Bloomington Stock Center; the Developmental Studies Hybridoma Bank; members of the Matunis lab for helpful discussion; Judy Qiu for generating FRT, ken recombinants; Rachel Stine for assistance with fly work; and Dr. Margaret de Cuevas and Rachel Stine for critical reading of the manuscript. This work was supported by NIH grant RO1HD40307 (E.M.)
PY - 2012/8/15
Y1 - 2012/8/15
N2 - Stem cells sustain tissue regeneration by their remarkable ability to replenish the stem cell pool and to generate differentiating progeny. Signals from local microenvironments, or niches, control stem cell behavior. In the Drosophila testis, a group of somatic support cells called the hub creates a stem cell niche by locally activating the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway in two adjacent types of stem cells: germline stem cells (GSCs) and somatic cyst stem cells (CySCs). Here, we find that ken and barbie (ken) is autonomously required for the self-renewal of CySCs but not GSCs. Furthermore, Ken misexpression in the CySC lineage induces the cell-autonomous self-renewal of somatic cells as well as the nonautonomous self-renewal of germ cells outside the niche. Thus, Ken, like Stat92E and its targets ZFH1 (Leatherman and Dinardo, 2008) and Chinmo (Flaherty et al., 2010), is necessary and sufficient for CySC renewal. However, ken is not a JAK-STAT target in the testis, but instead acts in parallel to Stat92E to ensure CySC self-renewal. Ken represses a subset of Stat92E targets in the embryo (Arbouzova et al., 2006) suggesting that Ken maintains CySCs by repressing differentiation factors. In support of this hypothesis, we find that the global JAK-STAT inhibitor Protein tyrosine phosphatase 61F (Ptp61F) is a JAK-STAT target in the testis that is repressed by Ken. Together, our work demonstrates that Ken has an important role in the inhibition of CySC differentiation. Studies of ken may inform our understanding of its vertebrate orthologue B-Cell Lymphoma 6 (BCL6) and how misregulation of this oncogene leads to human lymphomas.
AB - Stem cells sustain tissue regeneration by their remarkable ability to replenish the stem cell pool and to generate differentiating progeny. Signals from local microenvironments, or niches, control stem cell behavior. In the Drosophila testis, a group of somatic support cells called the hub creates a stem cell niche by locally activating the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway in two adjacent types of stem cells: germline stem cells (GSCs) and somatic cyst stem cells (CySCs). Here, we find that ken and barbie (ken) is autonomously required for the self-renewal of CySCs but not GSCs. Furthermore, Ken misexpression in the CySC lineage induces the cell-autonomous self-renewal of somatic cells as well as the nonautonomous self-renewal of germ cells outside the niche. Thus, Ken, like Stat92E and its targets ZFH1 (Leatherman and Dinardo, 2008) and Chinmo (Flaherty et al., 2010), is necessary and sufficient for CySC renewal. However, ken is not a JAK-STAT target in the testis, but instead acts in parallel to Stat92E to ensure CySC self-renewal. Ken represses a subset of Stat92E targets in the embryo (Arbouzova et al., 2006) suggesting that Ken maintains CySCs by repressing differentiation factors. In support of this hypothesis, we find that the global JAK-STAT inhibitor Protein tyrosine phosphatase 61F (Ptp61F) is a JAK-STAT target in the testis that is repressed by Ken. Together, our work demonstrates that Ken has an important role in the inhibition of CySC differentiation. Studies of ken may inform our understanding of its vertebrate orthologue B-Cell Lymphoma 6 (BCL6) and how misregulation of this oncogene leads to human lymphomas.
KW - Drosophila
KW - JAK-STAT
KW - Ken and barbie
KW - Niche
KW - Stem cell
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UR - http://www.scopus.com/inward/citedby.url?scp=84867910882&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2012.04.034
DO - 10.1016/j.ydbio.2012.04.034
M3 - Article
C2 - 22580161
AN - SCOPUS:84867910882
SN - 0012-1606
VL - 368
SP - 181
EP - 192
JO - Developmental biology
JF - Developmental biology
IS - 2
ER -