IISER Mohali researchers found molecule Lar as a localized factor that controls the exposure of the niche cells to insulin signaling and thereby controlling their proliferation and function.
In our body, stem cells and their progenitors are present in 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 the 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 ensures 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 a 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.