Poster Full Abstracts - Stem Cells
Poster board number is above title. The first author is the presenter
355
Klu might require additional co-factor proteins to regulate transcription of its target genes. Finally, loss- and gain-of-function analyses indicate that
klu
is
epistatic to
brat
. Together, these results lead us to propose that Brat-dependent inactivation of the Klu function provides a precise mechanism to distinguish
neuroblasts from intermediate neural progenitors ensuring a steady pool of neuroblasts and rapid generation of post-mitotic progeny during larval brain
neurogenesis.
836B
Piwi is a key regulator of the testicular stem cell niche in
Drosophila
.
Jacob M. Gonzalez, Haifan Lin. Yale Stem Cell Center, Yale University, New
Haven, CT.
The Piwi protein in
Drosophila
regulates a wide range of processes, which include transposon silencing, epigenetic programming, and stem cell self-
renewal. Our lab previously showed that Piwi functions are critical for niche signaling and intrinsic mechanisms to promote
Drosophila
ovarian germline
stem cell (GSC) division. Here we aim to clarify Piwi’s molecular activities in the niche of
Drosophila
testis stem cells. The conventional model for niche
function in the
Drosophila
testis is that a group of somatic cells called hub cells produce local signals to promote their adjacent stem cells to self-renew. Piwi
is expressed in both the germline and soma, which include the hub cells and somatic cyst stem cell (CySC) lineage. We showed that reducing levels of Piwi
in the hub cells via RNAi does not affect GSC maintenance or differentiation. Using cell-type-specific genetic mosaic analysis, we found that Piwi is
required autonomously for the maintenance of the two resident stem cell populations in the testis, GSCs and CySCs. Furthermore, we showed that germline
defects found in
piwi
mutant testis is rescued by restoring Piwi expression specifically and only in the CySCs, but not in the hub. Interestingly, reducing
levels of Piwi in CySCs causes a large expansion of stem cell-like cells. Our findings demonstrate that Piwi functions in CySCs nonautonomously regulate
GSC differentiation. We are currently investigating whether Piwi-mediated signaling from CySCs genetically interacts with key signaling pathways, such as
JAK-STAT or BMP, known to function in the male niche. Our work highlights the ability of Piwi to simultaneously serve as a cell-autonomous regulator for
one type of stem cell (i.e. GSC) and as a niche-signaling regulator from another type of stem cell (CySC). In addition, it illustrates a novel facet of the
complicated nature of the stem cell niche: one type of stem cell can serve as the niche signaling cells for a second type of stem cell in the same organ to
coordinate the self-renewal divisions and differentiation of adult stem cells.
837C
Asrij maintains the hematopoietic stem cell niche, controls blood cell homeostasis and is required for
Drosophila
immunity.
Rohan J. Khadilkar, Vani
Kulkarni, Srivathsa M.S., Maneesha S. Inamdar. Molecular Biology and Genetics Unit, JNCASR, Bangalore, Karnataka, India.
The lymph gland is the hematopoietic organ that orchestrates the second wave of hematopoiesis in
Drosophila
. A small group of signaling cells which
form the hematopoietic stem cell niche (Posterior Signaling Center) help in maintaining the hematopoietic progenitors in the medullary zone thereby
regulating hematopoietic differentiation in the cortical zone. The maintenance of the stem cell niche, precursor hemocytes and the differentiated hemocytes
is controlled by a host of conserved factors and signaling pathways but the mechanisms that modulate and integrate these signals are poorly understood. The
conserved endocytic protein Asrij maintains the Stem Cell Niche and controls differentiation during
Drosophila
lymph gland hematopoiesis.
asrij
null
mutants have a reduced niche, leading to loss of Domeless expression in the medullary zone and causing quiescent hemocyte precursors to differentiate
prematurely. Conversely, excess of
asrij
in the lymph gland causes expansion of the niche and reduces differentiation. Niche maintenance is regulated by
Serrate-mediated Notch signaling. Further
asrij
null mutants also show increase in crystal cell number, suggesting aberrant Notch signaling. Hence we
investigated the status of Notch in
asrij
null mutants.
asrij
null mutants show endocytic retention of Notch Intracellular Domain, resulting in a gain-of-
function phenotype and excess specification of crystal cells. Interestingly
asrij
null mutants also had reduced pro-phenoloxidase (PO) activity which could
be rescued by crystal cell rupture. This suggests that endocytic function of
asrij
is required for PO release. Taken together our data suggests a role for Asrij
in modulating signals that maintain the hematopoietic stem cell niche thereby affecting hemocyte differentiation.
838A
Control of
Drosophila
female germline stem cell niche formation by insulin signaling.
Chun-Ming Lai, Hwei-Jan Hsu. Institute of Cellular and
Organismic Biology, Academia Sinica, Taipei, Taiwan.
Stem cells are a small group of cells embedded in tissues with the capacity to produce differentiated cells for replenishing lost cells in fast-turnover or
damaged tissues, thereby maintaining tissue homeostasis. Stem cells reside in the stem cell niche, a specialized microenvironment, which provides both
physical contact and tissue-intrinsic signals to control stem cells. Stem cells and tumor cells share similar features of self-renewal and proliferation;
interestingly, a hypothesis of a latent tumor cell niche for tumor initiation is also proposed. The regulation of the stem cell niche itself, however, is poorly
understood. The
Drosophila
ovary is an excellent system to study stem cell biology, because of its ease of manipulation and well-characterized germline
stem cells (GSCs) and their niches. The GSC niche formed by terminal filament cells and cap cells houses two to three GSCs. We have previously shown
that insulin/insulin-like growth factor (IGF) signals mediate the effect of diet to directly control GSC niche cell survival. It is unclear, however, if
insulin/IGF signaling also controls the formation of the GSC niche. To examine this, we diminished the expression of the insulin receptor in the somatic cells
of developing ovaries using
UAS-RNAi
lines driven by specific
GAL4
drivers. Compared to the controls, flies that grew from insulin receptor-suppressed
larvae produced fewer progeny two days after eclosure and thereafter. In addition, we also observed that those flies carry small ovaries which are composed
of fewer ovarioles, functional units of ovaries, suggesting that insulin/IGF signaling controls the formation of terminal filament cells known to play a role in
subdividing the developing ovary into ovarioles. If insulin signaling controls cap cell formation and GSC recruitment, and the mechanisms underlying these
processes will be further investigated. Nevertheless, our results have provided new insights into the role of nutritional inputs on stem cell niche formation,
and that may eventually reveal therapeutic intervention for cancer.
839B
Activin signaling affects niche formation and stem cell establishment in the larval gonad through interaction with Ecdysone signaling.
Tamar Lengil,
Lilach Gilboa. Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
The step-by-step formation of a three-dimensional organ is one of the most complex processes within a developing organism. In particular, coordination
between proliferation and differentiation of the various cell types within the organ must be achieved. How such coordination is accomplished is largely