Need for preserving blood progenitors; Hox gene Ubx comes to the rescue

About Author: Aditya Kanwal belongs to Dharamshala city of Himachal Pradesh, India. He is an avid nature photographer and finds love in adventures. He completed his B.Tech in Biotechnology at Amity University, Noida. Followed by M.Tech in Biotechnology at MNNIT, Allahabad. Later, he joined as Ph.D. under the supervision of Dr. Lolitika Mandal, an Associate Professor in the Department of Biological Sciences, IISER Mohali. Drosophila melanogaster (fruit fly) used as a model to unravel the intricacies of myeloid hematopoiesis. In this article he talks about his work based on how “Ubx-Collier signaling cascade maintains blood progenitors in the posterior lobes of the Drosophila larval lymph gland” which was recently published in PLOS Genetics, reputed Scientific Journal.

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

Stem cells possess the ability to form a variety of mature cell types. However, these stem cells do require a specialized environment known as the niche cells for their maintenance and survival. The requirement of a niche was first hypothesized by Schofield in the late 1970s, based on the results obtained in his and the lab of his colleagues at that time. Discovered and experimentally validated first in Drosophila, since then, many stem cell – niche habitats have been found and worked out extensively in almost all model organisms.Owing to the importance of stem cells in disease and medicine, studying niche biology is essential.

In this study, we have identified and characterized a new niche defined by Hox gene Ultrabithorax (Ubx) in the hematopoietic organ of Drosophila larvae.This Ubx dependent signaling center maintains the reserve myeloid blood progenitors,kept aside for post-larval requirements. In conjunction with the previously established Hox gene Antennapedia (Antp) dependent niche in the thoracic lobe, this newly identified niche seems to have a two-tier control on the heterogenous progenitors present in the larval hematopoietic organ.

Infographic depiction to analogize stem cell-niche interaction.

How do these findings contribute to your research area?

The Drosophila larval hematopoietic organ spans from thoracic to abdominal segments in the larvae. From anterior to posterior direction, it can be divided into primary, secondary, and tertiary lobes. Previous work has established the presence of Hox gene Antp dependent niche/ signaling center in the anterior-most region or the primary lobe. This signaling centers known to maintain the proximal myeloid progenitors in the primary lobe.It is logical to believe that this multi-lobed organ that spans from thoracic to abdominal segments cannot be maintained by an anteriorly located niche. Through genetic and molecular approaches,our study identifies the Ubx signaling center and functionally demonstrates its role in maintaining posterior lobe blood progenitors. These blood progenitors in posterior lobes are crucial for post-larval requirements as they contribute to the hematopoiesis in adult Drosophila under normal conditions. Upon immune challenge, these progenitors proliferate and differentiate to form an arsenal against the invaders.

As the hematopoietic organ comprises of two signaling centers, it would be interesting to explore how they collaborate to maintain blood progenitors and influence each other during development and disorder.

What was the exciting moment during your research?

The presence of Hox gene Antp dependent signaling center in primary lobes was already known in the field. What was still unknown was that how the posterior lobe progenitors were maintained. The most exciting day for me was when I found that posterior lobes, which were believed to house only progenitors, harbor a progenitor-free Ubx domain. It was an indication that a cryptic domain might be an important component of the posterior lobes.

What do you hope to do next?

Next, I plan to pursue my Post-doctoral studies. Elucidating the Stem-cell niche interactions fascinates me, and I would like to follow it in higher model organisms for my future work.

Where do you seek scientific inspiration from?

I believe my scientific inspiration comes from my curiosity. Throughout my academic journey, my parents, teachers, and mentors have played significant roles in inculcating this attribute in me. Reading about scientific breakthroughs and discoveries further inspires me.

In the course of my Ph.D., the scientific environment and training provided by my Ph.D. supervisor, Dr. Lolitika Mandal have greatly helped me evolve as a researcher. Her fervor and never ending enthusiasm towards science keeps me motivated.

How do you intend to help Indian science improve?

There is a considerable disconnect between Science and Indian society. Most people are unaware of the kind of work that goes on in the labs of scientists, and as a result,the general public does not value science deeply. I would try my best to reduce this divide, and one way to do that is by popularizing science for the public.

Furthermore, I intend to be a part of the Indian education system in the future. I believe it’s imperative to instill scientific intent in school kids as well as young graduates. India has some of the brightest minds and hardworking people. Making kids realize the importance of science will encourage more of them to pursue scientific research as a career choice.

Aditya and Dr. L. Mandal

Reference

Kanwal A, Joshi PV, Mandal S, Mandal L (2021) Ubx-Collier signaling cascade maintains blood progenitors in the posterior lobes of the Drosophila larval lymph gland. PLOS Genetics 17(8): e1009709. https://doi.org/10.1371/journal.pgen.1009709

Edited by: Nikita Nimbark

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