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Stem Cell Niche Employs A Rheostat To Control Insulin Signaling

IISER Mohali researchers found molecule Lar as a localized factor that controls the exposure of the niche cells to insulin signalling and thereby controlling their proliferation and function.

FEB 17, 2020 | BY RATNESHWAR THAKUR

In our body, stem cells and their progenitors are present in a particular microenvironments or niches- an environment with unique chemical and physical properties. Usually, Cells present in our body have specific roles, but stem cells are the cells that do not yet have any specific role and can become almost any cell by the process of differentiation.

Stem cells and progenitor cells are regulated by systemic factors as well as local stem cell niche-derived factors. Stem and progenitor cells residing within a niche are shielded off from signals that push them towards differentiation. Thus, their state and fate are maintained if they are housed within a niche. However, how systemic and localized niche signals collaborate in achieving normal tissue functioning is not well known.

Now a research team led by Dr. Lolitika Mandal at Indian Institute of Science Education and Research (IISER- Mohali) - have uncovered a novel function of Lar (leucocyte antigen like protein) that expresses in the blood stem cell niche. Lar acts as a rheostat to harmonize with insulin signalling which ensure normal functioning of the stem cell niche in Drosophila blood forming organ (Lymph gland). The results of this study were published in the journal Development.


"While the rest of the world is exploring to understand the factors required for maintaining stemness, our laboratory aims to understand what it takes to build up a niche. We have conducted a genome-wide screen and have been successful in pinning down some candidates critical for niche maintenance," says Dr. Lolitika Mandal, Developmental Biologist at IISER, Mohali.

In this study, researchers found molecule Lar as a localized factor that empowers niche to estimate the physiological state of an organism. They observed, Lar protein controls the exposure of the niche cells to insulin signalling and thereby controlling their proliferation and function.

"Our genetic and expression studies along with biochemical analyses demonstrated a clear interaction of Lar with Insulin Receptor. We found loss of Lar from the niche cells elicited an immune response even without any infection. Further, in our study Loss of Lar protein from niche hyperactivated insulin signalling," said Harleen Kaur, lead author of this study. "The moment we realized that we are answering a fundamental cell biological question; it all together became more exciting. However, we are left to show whether Lar plays a similar role in our case too," she added.




The study is significant, and especially for diseases where there is a rise in factors of systemic signals, the modulation at known local factors would be useful for designing therapeutic interventions.

"The recent work from Dr. Lolitika Mandal has unravelled a negative regulator of nutrition sensing pathway, insulin-like signalling pathway, which keeps a check on the proliferation of hemocytes. This is an important discovery, which will provide a handle to study further the regulation of Hematopoiesis," said Prof. L. S. Shashidhara (currently on lien to Ashoka University, Sonepat), Scientist at IISER-Pune. He was not involved in this study.


The research team included Harleen Kaur, Shiv Kumar Sharma, Sudip Mandal, Lolitika Mandal. The study was funded by Department of Science and Technology (DST), Government of India, Council of Scientific and Industrial Research (CSIR) and Wellcome Trust DBT India Alliance.


Journal Reference:
Lar maintains the homeostasis of the hematopoietic organ in Drosophila by regulating insulin signaling in the niche





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Ratneshwar Thakur
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