Biology subjects

Krasovec, G.

Publications and source records attributed to Krasovec, G..

2 recordsLinked to original sources

bioRxiv2022

Senescence-induced cellular reprogramming drives cnidarian whole-body regeneration

Cell fate stability is essential to maintaining law and order in complex animals. However, high stability comes at the cost of reduced plasticity and, by extension, poor regenerative ability. This evolutionary trade-off has resulted in most modern animals being rather simple and regenerative or complex and non-regenerative. The mechanisms mediating cellular plasticity and allowing for regeneration remain unknown. We show that signals emitted by senescent cells can destabilize the differentiated state of neighboring somatic cells, reprogramming them into stem cells that are capable of driving whole-body regeneration in the cnidarian Hydractinia symbiolongicarpus. Pharmacological or genetic inhibition of senescence prevented reprogramming and regeneration. Conversely, induction of transient ectopic senescence in a regenerative context resulted in supernumerary stem cells and faster regeneration. We propose that senescence signaling is an ancient mechanism mediating cellular plasticity. Understanding the senescence environment that promotes cellular reprogramming could provide a new avenue to enhance regeneration.

developmental biology↗

bioRxiv2021

Intrinsic apoptosis is evolutionary divergent among metazoans

Apoptosis is regulated cell death that depends on caspases. Upstream of each apoptotic signalling pathway is involved a specific initiator caspase. Characterised in nematode, fly and mammals, intrinsic apoptosis is considered to be ancestral and conserved among animals, and depends on shared initiators; caspase-9, Apaf-1 and Bcl-2. However, the biochemical role of mitochondria, the pivotal function of cytochrome c and the modality of caspase activation remain highly heterogeneous and hide profound molecular divergences among apoptotic pathways in animals. Uncovering the phylogenetic history of apoptotic actors, especially caspases, is crucial to shed light on intrinsic apoptosis evolutionary history. Here, we demonstrate by phylogenetic analyses, that caspase-9, the fundamental key of intrinsic apoptosis, is deuterostome-specific, while caspase-2 is ancestral to bilaterians. Our analysis of Bcl-2 and Apaf-1 confirm heterogeneity in functional organisation of apoptotic pathways in animals. Our results support emergence of distinct intrinsic apoptotic pathways during metazoan evolution.

evolutionary biology↗