Molecular identity of nucleotide factor(s) that serve as trigger for the activation of cell-cycle progression in adult stem cells or human mesenchymal stem cells (hMSCs) or progenitor cells is not well understood. Recent studies highlight the importance of extracellular nucleotide-triphosphates (eNTPs) like ATP as key regulators of various functions executed by the adult stem cells. It has long been speculated that discrete release of ATP by the cells in response to shear stress plays a major role in the initiation of various physiological processes such as proliferation, repair and regeneration, migration and homing. eNTPs acts via purinoceptors (P2Y) and multiple isoforms of P2Y receptor are expressed in all the cells, the molecular mechanisms of P2Y-signaling still remain unexplored. On certain stimuli, hMSCs release ATP constitutively and ATP activates variety of P2X/P2Y receptors in MSCs inducing robust Ca2+ responses from different tissues/species and calcium mediated functional responses in hMSCs were considered as predominant one. The mechanism of storeoperated Ca2+ entry through which the intracellular calcium concentration is restored plays a major role in that. Yet the cognate intrinsic mechanisms of these purinergic receptors remain contentious. Our interest is to understand the basic mechanisms under which the stem cells perform their functions by strengthening the signaling cascades and genetic transcription effected by activation of purinoceptors.