The Endosomal Sorting Complex, ESCRT, has diverse roles in blood progenitor maintenance, lineage choice and immune response.
Title | The Endosomal Sorting Complex, ESCRT, has diverse roles in blood progenitor maintenance, lineage choice and immune response. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Ray A, Rai Y, Inamdar MS |
Journal | Biol Open |
Volume | 13 |
Issue | 6 |
Date Published | 2024 Jun 15 |
ISSN | 2046-6390 |
Keywords | Animals, Cell Differentiation, Cell Lineage, Drosophila, Drosophila Proteins, Endosomal Sorting Complexes Required for Transport, Hematopoietic Stem Cells, Immunity, Signal Transduction |
Abstract | Most hematological malignancies are associated with reduced expression of one or more components of the Endosomal Sorting Complex Required for Transport (ESCRT). However, the roles of ESCRT in stem cell and progenitor maintenance are not resolved. Parsing signaling pathways in relation to the canonical role of ESCRT poses a challenge. The Drosophila hematopoietic organ, the larval lymph gland, provides a path to dissect the roles of cellular trafficking pathways such as ESCRT in blood development and maintenance. Drosophila has 13 core ESCRT components. Knockdown of individual ESCRTs showed that only Vps28 and Vp36 were required in all lymph gland progenitors. Using the well-conserved ESCRT-II complex as an example of the range of phenotypes seen upon ESCRT depletion, we show that ESCRTs have cell-autonomous as well as non-autonomous roles in progenitor maintenance and differentiation. ESCRT depletion also sensitized posterior lobe progenitors to respond to immunogenic wasp infestation. We also identify key heterotypic roles for ESCRT in position-dependent control of Notch activation to suppress crystal cell differentiation. Our study shows that the cargo sorting machinery determines the identity of progenitors and their adaptability to the dynamic microenvironment. These mechanisms for control of cell fate may tailor developmental diversity in multiple contexts. |
DOI | 10.1242/bio.060412 |
Alternate Journal | Biol Open |
PubMed ID | 38828842 |
PubMed Central ID | PMC11212638 |
Grant List | EMR/2016/000641 / / Science and Engineering Research Board / JCB/2019/000020 / / JC Bose fellowship, Department of Science and Technology, Government of India / / / LSRET from Department of Biotechnology and Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) / EMR/2016/000641 / / SERB / JCB/2019/000020 / / JC Bose / / / Department of Science and Technology, Government of India, LSRET / / / Jawaharlal Nehru Centre for Advanced Scientific Research / |