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Leanne Jones

 

Leanne Jones

Leanne Jones

Assistant Professor
William Scandling Developmental Chair
Laboratory of Genetics

"The behavior of stem cells is regulated both by intrinsic factors within the stem cells and extrinsic factors from the surrounding environment, known as the stem cell niche. I am interested in how the relationship between stem cells and their environment changes during development, aging, and tumorigenesis."

Just as in many other tissues, the stem cells in fruit fly testes reside within a specialized environment, commonly known as the stem cell niche. The Jones lab is particularly interested in understanding how the niche shelters adult stem cells and provides factors necessary to keep them young and vital. In a line of reasoning reminiscent of the chicken and egg question, investigators long thought that the allotment of cells making up a fruit fly's niche was handed out at birth and meant to last a lifetime. Leanne Jones found that this may not always be the case.

Using microscopy and fluorescent markers enabling them to image specific cell types over time, Jones's team actually caught a testis stem cell population in the act of turning into its own niche cells, known in the fly testis as the hub. The hub contains approximately ten cells that produce factors that promote self-renewal of two neighboring stem cell populations—germline stem cells, which become sperm, and somatic stem cells (SSCs), which develop into a structure that encapsulates maturing sperm. After tracking individual cells over a period of days, the researchers saw that SSCs have the remarkable ability to generate other SSCs as well as their own niche support cells. By contrast, germline stem cells do not generate hub cells. Biochemical studies provided further circumstantial support for the idea that hub cells emerge from SSCs.

The fact that the cells that comprise a specialized niche in the testes of fruit flies actually emerge from adult stem cells has implications for regenerative medicine, aging research, and cancer therapeutics. It raises the question of whether stem cells transplanted in proposed regeneration therapies will establish their own support crew, or whether a "niche transplant" will be required to maintain them. Or, do so-called cancer stem cells, which are thought to form the root of most tumors, create a structure analogous to the niche, and if they do, could it be targeted as anti-cancer therapy?

Lab Photo

Left to right:
Back row: Michael Rocha, Justin Voog, Catherine McLeod, Grant Miura, William Ansari, Darrell Tran Front row: Cecilia D'Alterio, Noel Moya, Leanne Jones, Chi Wong, Severine Landais, Monika Boyle, Hila Toledano-Katchalski

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Leanne Jones

Faculty

Leanne Jones

Leanne Jones

Assistant Professor
William Scandling Developmental Chair
Laboratory of Genetics

Stem cells are the building blocks during development of organisms as varied as plants and humans. In addition, stem cells provide for the maintenance and regeneration of tissues, such as blood and skin, throughout the lifetime of an individual. The ability of stem cells to contribute to these processes depends on their ability to divide and generate both new stem cells (self-renewal) as well as specialized cell types (differentiation). Stem cells lose the potential for continued self-renewal when removed from their normal cellular environment, known as the stem cell "niche," suggesting an essential role for the niche in controlling stem cell behavior.

The Jones lab is using the process of spermatogenesis in Drosophila melanogaster as a model system to establish paradigms for how stem cell behavior is controlled. Stem cells can be easily located at the tip of the Drosophila testis; therefore, it is possible to study these cells in the context of their normal environment without destroying the tissue. Being able to study the behavior of stem cells in vivo allows us to begin to ask questions about how the niche can control stem cell self-renewal and survival and how the relationship between stem cells and the niche evolves during development, as a consequence of aging, and during tumor initiation and progression.

Age-related changes to stem cells and the stem cell niche

Loss of tissue and organ function is a characteristic of aging, and such changes have been attributed to decreases in stem cell function. Given the relationship between reduced stem cell activity, loss of tissue homeostasis, and aging, several key questions emerge. Is loss of tissue homeostasis due to 1) a decrease in stem cell number 2) an inability of stem cells to respond to appropriately to signals from the niche 3) reduced signaling from the niche to specify stem cell self-renewal and maintenance or 4) reduced progenitor cell function? If all of these factors contribute to loss of tissue homeostasis, is any one more prevalent than the others, and which changes could be most easily targeted in the treatment of aging-related diseases? Lastly, can loss of tissue homeostasis be uncoupled from the aging process and studied independently with respect to changes in stem cell function?

Data from our lab suggest that aging of the stem cell niche is a major factor in decreased stem cell activity and tissue homeostasis over time. Therefore, we predict that when considering transplantation of stem cells, it may be necessary to transplant niche cells, in addition to stem cells, to provide a "younger" niche that may be more capable of sustaining stem cell self-renewal. Furthermore, as one of the primary risk factors for the development of cancer is increased age, these studies will reveal the consequences of aging on the regulation of tissue stem cell behavior and may highlight some of the factors that lead to the transformation of normal stem cells into cancer stem cells over time.

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