TY - JOUR T1 - DDX24 is required for muscle fiber organization and the suppression of wound-induced Wnt activity necessary for pole re-establishment during planarian regeneration. JF - Dev Biol Y1 - 2022 A1 - Sarkar, Souradeep R A1 - Dubey, Vinay Kumar A1 - Jahagirdar, Anusha A1 - Lakshmanan, Vairavan A1 - Haroon, Mohamed Mohamed A1 - Sowndarya, Sai A1 - Sowdhamini, Ramanathan A1 - Palakodeti, Dasaradhi AB -

Planarians have a remarkable ability to undergo whole-body regeneration. Successful regeneration outcome is determined by processes like polarity establishment at the wound site, which is followed by pole (organizer) specification. Interestingly, these determinants are almost exclusively expressed by muscles in these animals. However, the molecular toolkit that enables the functional versatility of planarian muscles remains poorly understood. Here we report that SMED_DDX24, a D-E-A-D Box RNA helicase, is necessary for planarian survival and regeneration. We found that DDX24 is enriched in muscles and its knockdown disrupts muscle fiber organization. This leads to defective pole specification, which in turn results in misregulation of many positional control genes specifically during regeneration. ddx24 RNAi also upregulates wound-induced Wnt signalling. Suppressing this ectopic Wnt activity rescues the knockdown phenotype by enabling better anterior pole regeneration. To summarize, our work highlights the role of an RNA helicase in muscle fiber organization, and modulating amputation-induced wnt levels, both of which seem critical for pole re-organization, thereby regulating whole-body regeneration.

VL - 488 ER - TY - JOUR T1 - S. mediterranea ETS-1 regulates the function of cathepsin-positive cells and the epidermal lineage landscape via basement membrane remodeling. JF - J Cell Sci Y1 - 2022 A1 - Dubey, Vinay Kumar A1 - Sarkar, Souradeep R A1 - Lakshmanan, Vairavan A1 - Dalmeida, Rimple A1 - Gulyani, Akash A1 - Palakodeti, Dasaradhi KW - Animals KW - Basement Membrane KW - Cathepsins KW - Cell Differentiation KW - Epidermis KW - Humans KW - Matrix Metalloproteinases KW - Mediterranea KW - Planarians KW - Transcription Factors AB -

Extracellular matrix (ECM) is an important component of stem cell niche. Remodeling of ECM mediated by ECM regulators, such as matrix metalloproteinases (MMPs) plays a vital role in stem cell function. However, the mechanisms that modulate the function of ECM regulators in the stem cell niche are understudied. Here, we explored the role of the transcription factor (TF) ETS-1, which is expressed in the cathepsin-positive cell population, in regulating the expression of the ECM regulator, mt-mmpA, thereby modulating basement membrane thickness. In planarians, the basement membrane around the gut/inner parenchyma is thought to act as a niche for pluripotent stem cells. It has been shown that the early epidermal progenitors migrate outwards from this region and progressively differentiate to maintain the terminal epidermis. Our data shows that thickening of the basement membrane in the absence of ets-1 results in defective migration of stem cell progeny. Furthermore, the absence of ets-1 leads to a defective epidermal progenitor landscape, despite its lack of expression in those cell types. Together, our results demonstrate the active role of ECM remodeling in regulating tissue homeostasis and regeneration in the planarian Schmidtea mediterranea. This article has an associated First Person interview with one of the co-first authors of the paper.

VL - 135 IS - 20 ER - TY - JOUR T1 - Mitochondrial state determines functionally divergent stem cell population in planaria. JF - Stem Cell Reports Y1 - 2021 A1 - Mohamed Haroon, Mohamed A1 - Lakshmanan, Vairavan A1 - Sarkar, Souradeep R A1 - Lei, Kai A1 - Vemula, Praveen Kumar A1 - Palakodeti, Dasaradhi AB -

Mitochondrial state changes were shown to be critical for stem cell function. However, variation in the mitochondrial content in stem cells and the implication, if any, on differentiation is poorly understood. Here, using cellular and molecular studies, we show that the planarian pluripotent stem cells (PSCs) have low mitochondrial mass compared with their progenitors. Transplantation experiments provided functional validation that neoblasts with low mitochondrial mass are the true PSCs. Further, the mitochondrial mass correlated with OxPhos and inhibiting the transition to OxPhos dependent metabolism in cultured cells resulted in higher PSCs. In summary, we show that low mitochondrial mass is a hallmark of PSCs in planaria and provide a mechanism to isolate live, functionally active, PSCs from different cell cycle stages (G0/G1 and S, G2/M). Our study demonstrates that the change in mitochondrial metabolism, a feature of PSCs is conserved in planaria and highlights its role in organismal regeneration.

VL - 16 IS - 5 ER -