Souradeep Sarkar

All Publications

• Smed-ETS-1 regulates cathepsin+ cell function and epidermal lineage landscape via basement membrane remodeling. Journal of cell science Dubey, V. K., Sarkar, S. R., Lakshmanan, V., Dalmeida, R., Gulyani, A., Palakodeti, D. 2022

  Abstract

  Extracellular matrix (ECM) is an important component of stem cell niche. Remodelling of ECM mediated by ECM regulators such as 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 expressed in the cathepsin+ 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 outward from this region and progressively differentiate to maintain the terminal epidermis. Our data shows thickening of basement membrane in the absence of ets-1 results in defective migration of stem cells progeny. Furthermore, the absence of ets-1 led to a defective epidermal progenitor landscape, in spite of its lack of expression in those cell types. Together, our results demonstrate the active role of ECM remodelling in regulating tissue homeostasis and regeneration in planaria.

  View details for DOI 10.1242/jcs.259900

  View details for PubMedID 36172824

• DDX24 is required for muscle fiber organization and the suppression of wound-induced Wnt activity necessary for pole re-establishment during planarian regeneration DEVELOPMENTAL BIOLOGY Sarkar, S. R., Dubey, V., Jahagirdar, A., Lakshmanan, V., Haroon, M., Sowndarya, S., Sowdhamini, R., Palakodeti, D. 2022; 488: 11-29

  Abstract

  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.

  View details for DOI 10.1016/j.ydbio.2022.04.011

  View details for Web of Science ID 000804943300002

  View details for PubMedID 35523320

• Mitochondrial state determines functionally divergent stem cell population in planaria STEM CELL REPORTS Haroon, M., Lakshmanan, V., Sarkar, S. R., Lei, K., Vemula, P., Palakodeti, D. 2021; 16 (5): 1302-1316

  Abstract

  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.

  View details for DOI 10.1016/j.stemcr.2021.03.022

  View details for Web of Science ID 000649799600003

  View details for PubMedID 33861990

  View details for PubMedCentralID PMC8185449