Stem Cell Quiescence in the Drosophila Lymph Gland
Mondal et al Banerjee. Submitted in Review. Interaction between niche and equilibrium signals in homeostatic control of stem cell quiescence.
Jung, Evans, Uemura, & Banerjee.2005. The Drosophila lymph gland as a developmental model of hematopoiesis. Development 132 (11).
Mandal et al Banerjee 2007. A hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors. Nature 466.
Dr. Banerjee can you please tell us a bit about yourself, your career path over the years and how you began studying of stem cells regulation in Drosophila?
Referring to your paper titled, “Interaction between niche and equilibrium signals in homeostatic control of stem cell quiescence”, what is the exact sequence of events during the development of the lymph gland with respect to the various signalling pathways? As I understand it, Hh is the first morphogen to be released early on in development by the PSC, creating a ‘niche signalling’ pathway, but how does the sequence of signalling pathways then proceed to give rise to the ‘equilibrium signalling’ pathways? Is there a dominant pathway?
The papers suggest that MZ is the site for stem cell maintenance, and CZ is the site for hemocyte maturation. However, PSC has been discovered to only regulate the maintenance of stem cells in the MZ. Figures from schematic representations and microscopic pictures show that PSC in fact comes in contact with both the MZ and CZ. Therefore, is it a possibility that PSC is actually regulating this whole orchestra? Suppressing differentiation in MZ and promoting it in CZ?
Gwen Nguyen Huynh
In your letter, “A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors,” you hypothesize that Hh could be transported via these projections you observed extending from the PSC to the MZ. Would it be possible to tag Hh in conjunction with labeling these projections with GFP to test this hypothesis?
Why would overexpression of Antp within the PSC result in two or three large cell clusters over a large volume rather than the single, dense population seen in wild type?
Kim Chi Ngo
If Hypoxia inducible factor α (HIF α) regulates proliferation and differentiation of haematopoietic stem cells, what is the optimal oxygen concentration for stem cell niche (what is the oxygen concentration within the zygote)? Also, what is the role of oxygen in stem cell modulation and differentiation?
One subject your draft article brings to mind is how the body regenerates in response to injury to differentiated cells. If differentiated cells contribute to progenitor quiescence, then one might expect the loss of differentiated cells to induce proliferation to replace the lost cells. However, in the Drosophila lymph gland, absence of the signals produced by the differentiated cortical cells seems only to induce progenitor cell differentiation, not proliferation. Can you comment on this? Is loss of differentiated cell signaling known to play a role in proliferation (and response to injury) in other model systems?
In your article concerning the interaction between niche and equilibrium signals in homeostatic control of stem cell quiescence, you discuss the factors that maintain stem-like progenitors in vivo. However, when stem cells and their progenitor cells are in culture, do you think that the lack of a niche affects their ability to retain this quiescent state? What keeps cells quiescent in culture or stimulates them to self replicate?
In “A Hedgehog- and Antennapedia-dependent niche maintains Drosophila haematopoietic precursors”, Atennapedia overexpression was linked to increased quiescence among Hemopoetic progenitor cells. Could Atnp expression realistically be manipulated in mature niches as a method to slow lymphatic cancers?
How important do you feel the study of stem cell niches will be to the advancement of regenerative medicine? In addition, do you feel that there is a special importance to regenerative medicine that can be attributed to one type of stem cell niche (Haemopoietic, Mesenchymal, gut, neural, etc) over any others?
Follow up question: Would you explain how blood marrow transplants work, and the impact it has had on human health? Moreover, how do you see our current understanding of Haematopoietic stem cells changing or impacting blood based regenerative medicine?
Kim Chi Ngo
Knowing the positive potential of studying human embryonic stem cells, what do you think about the current court case that is going on, two plaintiffs being James Sherley and Theresa Deisher, adult stem cell researchers, whose lawsuit caused a halting of federal funding for human embryonic stem cell research? How do think current and future research and medicine will be impacted by this case?
Hyunwon (Sylvie) Bae
How would you compare an adult hemocyte, which matured inside the lymph gland, to an adult hemocyte that has been produced using IPS technology? Would you ever use IPS cells in your research? If so, why would these cells further your research which largely takes place in vivo? If not, why would you feel this way?
The “equilibrium signal” that maintains the stem cell’s quiescence reminds of several differential expression-based processes, such as Darwin’s finches and BMP4. What evolutionary implications might this process entail? How can this regulation be beneficial to the organism?
Currently in your opinion what are the most pressing questions in the study of the stem cell regulation in the haematopoietic niche, and what steps is your lab taking to address these questions?