Tissue homeostasis from stemcells.
Many highly specialized cells, such as blood, skin, or sperm cells, are short-lived and need to be constantly reproduced from so-called adult stem cells. Stem cell maintenance and fgermline differentiation depends on intrinsic cues and on external signals provided by the cellular microenvironment.
The cellular microenvironment/niche
One aspect of our research focuses on the mechanisms that regulate the formation and function of the cellular microenvironment. In Drosophila testes, the germ line stem cells are associated with cyst stem cells, and the differentiating germline cells are associated with cyst cells. We have implicated several signaling pathways, including signaling via epidermal growth factor and Ecdyson, in regulating these microenvironment cells and in their interaction with early stage germline.
Figure legend: At the tip of the male Drosophila gonad, the germline stem cells (blue) contact hub cells (red) and are enclosed in somatic cyst stem cells (yellow). Stem cells daughters that are displaced away from the hub (purple) become enclosed by two cyst stem cell daughters, the cyst cells (orange), and initiate differentiation.
Germline stem cell activity
Our research has recently expanded towards investigating the regulation of germline stem cell divisions. We have discovered that germline stem cells can respond to a demand for specialized cells. When males are repeatedly mated, they increase the division frequency of their germline stem cells. This response is dependent on G-protein signaling.
Figure legend: Each germline stem cell division produces exactly 64 sperm cells. When males are challenged to produce more sperm, the germline stem cells increase their division frequency.
Prospect: The outcome of our research shall shed light on the mechanisms that regulate stem cells, and at the same time contribute to the development of techniques for stem cell therapy. In the future, stem cell therapy may be applied to a wide range of human disorders, including many types of cancer, spinal cord injuries, diabetes, and neurological diseases such as Parkinson's Disease.
Tissue replenishment from stem cells, Epidermal Growth Factor Receptor, germ cell tumor, stem cell self-renewal
Malpe, M., and Schulz, C. (2020). The impact of genetic background and gender in the increase in mitotic index in response to mating of Drosophila melanogaster. BioRxiv, doi: https://doi.org/10.1101/2020.05.15.098509.
Malpe, M., McSwain, L.F., Ng, C., Kudyba, K., Nicholson, J., Brady, M., Parrott, B.B., Choksi, V., Hudson, A.G., and Schulz, C. (2020). G-Protein signaling is required for increasing germline stem cell division frequency in response to of mating in Drosophila males. Scientific Reports 10, Article number: 3888.
Chun, Ng., Qian Y., and Schulz, C. (2019) Notch and Delta are required for survival of the germline stem cell lineage in testes of Drosophila melanogaster. PLoS One 14(9):e0222471.
Qian, Y., Ng, C. L., Schulz, C. (2015) CSN maintains the germline cellular microenvironment and controls the level of stem cell genes via distinct CRLs in testes of Drosophila melanogaster. Dev. Biol. 398 (1): 68-79.
Qian, Y, Dominado, N., Zoller, R., Ng,R., Kudyba, K., Siddall, N. A, Hime, G. R, Schulz, C (2014). Ecdysone signaling antagonizes Epidermal Growth Factor signaling in regulating cyst differentiation in the male gonad of Drosophila melanogaster. Dev. Biol. 394 (2): 217-227.
Hudson, A., Parrott, B.B., Qian, Y., Schulz, C. (2013). A temporal signature of Epidermal Growth Factor signaling regulates early steps of tissue homeostasis in testes of Drosophila melanogaster. PLoS ONE 8(8): e70678DOI: 10.1371/journal.pone.0070678.
Zoller, R, Schulz C. (2012) The Drosophila Cyst Stem Cell Lineage – Partners Behind The Scene? Spermatogenesis 2 (3): 1-13.
Parrott, B. B., Hudson, A., Brady, R., Schulz, C. (2012) Control of Germline Stem Cell Division Frequency – A Novel, Developmentally Regulated Role for Epidermal Growth Factor Signaling. PLoS ONE 7(5): e36460. doi:10.1371/journal.pone.0036460
Parrott B. B., Chiang, Y., Hudson, A., Sarkar, A., Guichet, A., and Schulz, C. (2011) Nucleoporin98-96 Function Is Required For Transit Amplification Divisions in the Germ Line of Drosophila melanogaster. PLos one http://dx.plos.org/10.1371/journal.pone.0025087.
Sarkar, A., Parikh, N., Hearn, S. A., Fuller, M. T., Tazuke, S. I., and Schulz, C. (2007) Antagonistic roles of Rac and Rho in organizing the germ cell micro-environment. Curr. Biol. 17, 1253-1258.
Sarkar, A., and Schulz C. (2007) An approach for Immunofluorescence of Drosophila S2 cells. CSH Protocols; doi:10.1101/pdb.prot4760.
Schulz, C. (2007) Making it to the top 100 – in situ hybridization to Drosophila testes. CSH Protocols, doi:10.1101/pdb.prot4764.
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Schulz, C., Wood, C. G, Jones, D. L., Tazuke, S. I. & Fuller, M.T. (2002) Signaling from germ cells mediated by the rhomboid homologue stet organizes encapsulation by somatic support cells. Development 129, 4523-4534.
Tazuke S. I, Schulz C, Gilboa L., Mahowald, A.P.,Guichard, A, Ephrussi, A., Fogarty, M., Wood, C., Lehmann, R. & Fuller, M.T. (2002) A germline-specific gap junction protein required for survival of differentiating early germ cells. Development 129, 2529-2539.
Schulz, C., Perezgasga, L. & Fuller, M.T. (2001) Genetic analysis of dPsa, the Drosophila orthologue of puromycin-sensitive aminopeptidase, suggests redundancy of aminopeptidases. Dev. Genes & Evol. 211, 581-588.
Kiger, A. A., Jones, D. L, Schulz, C., Rogers, M.B. & Fuller, M.T. (2001) Stem Cell Self-Renewal Specified by JAK-STAT Activation in Response to a Support Cell Cue. Science 294, 2542-2545.