Stem cell being a controlling mother!

Work done in the lab of Dr. Krishanu Ray at Tata Institute of Fundamental Research

About author

Dr. Purna Gadre did her Bachelor’s in Biotechnology from Ramnarain Ruia College, Mumbai University. She got her master’s in Biotechnology from IIT Bombay, where she received a silver medal form her institute. She subsequently joined Prof. Krishanu Ray’s laboratory at Tata Institute of Fundamental Research as a Ph.D. student. In her doctoral work, Purna studied the regulation of germline stem cell division and that of its progeny in Drosophila. Her recent paper shows that the germline cell cycle alters along with cell differentiation in Drosophila testis. Further, this study suggests that the germline stem cells can control the cell division rates and the terminal differentiation of their progeny. This collaborative work also presents a computational method to estimate the cell division rates of any stem cell system at a steady-state, which will prove highly useful for any stem cell biologist.

Tata Institute of Fundamental Research

Interview

How would you explain your research outcomes to the non-scientific community?

Most of us know stem cells as the ultimate mother cells, which can divide and specialize into any cell from our body. However, adults also have “adult” stem cells which keep dividing throughout their lives. We have hair root stem cells forming hair, blood stem cells forming all blood and immune cells, germline stem cells forming eggs/ sperms, etc.

By fitting the biology of stem cell divisions into mathematics, we came up with a method to calculate the time taken by stem cells and their daughters to divide, in the fruit fly testis. We show that, along their journey to becoming specialized cells, the stem cell daughters alter their speed of cell division. The first few daughters divide slowly, after which they double their speed of division. We also show that the stem cells can control the time taken by their daughters to divide and eventually specialize. Thus, these stem cells have the potential to act as master regulators, controlling organ size.

This is a diagram of the tip of the fruit fly testis, where a germline stem cell (GSC) divides four times to form 1-cell gonialblast (GB), 2cell, 4cell, 8cell and 16-cells. The equation depicted at the top was used for calculating lifespans (cell division time) from demography (germline population statistics). N’s represent the number of alive germ cells at each stage, D’s represent the number of dead germline cells and T’s represent the cell division time. The plot shows that increase in cell division time in the early stem cell daughters followed by a decrease. Source: Gadre et al, iScience, 2021 https://doi.org/10.1016/j.isci.2021.103232

How do these findings contribute to your research area?

Regulation of cell division is essential during organogenesis and in fully-functional organs to produce the required number of cells according to physiological needs. In multiple epithelial systems, stem cells are located near the blood vessels, making them more sensitive to systemic signals. Our work suggests that stem cells can control the proliferation (cell division) rates of their daughters, suggesting that stem cells can act as “contact points” relaying the physiological information to their daughters, regulating the homeostasis of the whole organ. Further, we present a computation method to predict the cell division time of the stem cells and their daughters. Due to the ease of experimental paradigm, this method can be adapted to any other stem cell system. This method will enable the study of how different environmental and intrinsic factors control the cell cycle rate of the stem cell lineage, thus becoming a valuable tool for stem cell biology and therapeutics.

“We also show that the stem cells can control the time taken by their daughters to divide and eventually specialize. Thus, these stem cells have the potential to act as master regulators, controlling organ size.”

What was the exciting moment during your research?

There wasn’t one EUREKA moment, but the whole journey of this interdisciplinary collaboration was beautiful. I think the most memorable moment during this work was when we could actually see the dividing germline cells under a microscope, and that too inside an alive testis!

I also immensely enjoyed looking at a biological system from a mathematician’s point of view. While trying to fit the biology of the germline stem cell lineage into mathematics, I feel I understood this biological system even better.

What do you hope to do next?

We are currently looking at how the germline cell cycle rates are altered by neighboring tissue. During my postdoctoral training in future, I wish to study how physiological signals such as diet, hormones, etc., control stem cell divisions and differentiation.

Where do you seek scientific inspiration from?

Like any other scientist, I get inspired by unsolved mysteries. I believe in the philosophy that if you pay enough attention, every person that you meet teaches you something. During my scientific journey, I have been inspired not only by beautifully written and executed scientific studies but also by my Professors, peers, and even society in general. In 2018, I delivered a lecture to higher secondary school kids on developing scientific temperament. I can never forget their starry-eyed wonder; it motivates me to study and investigate new mysteries every day.

How do you intend to help Indian science improve?

During my PhD days in TIFR, I have been fortunate enough to discuss TIFR science with school kids from all around Maharashtra during Frontiers of Science Open day organized every year. In future, I hope to continue to engage in public outreach activities such as writing blogs, discussing scientific advances to inspire young Indian minds towards scientific research.

Reference

Purna Gadre, Nitin Nitsure, Debasmita Mazumdar, Samir Gupta, Krishanu Ray. The rates of stem cell division determine the cell cycle lengths of its lineage. iScience, 24, 11, 2021, 103232, https://doi.org/10.1016/j.isci.2021.103232.

Edited by: Dolly Singh