Biology subjects

Bartscherer, K.

Publications and source records attributed to Bartscherer, K..

3 recordsLinked to original sources

bioRxiv2022

An ERK-dependent molecular switch antagonizes fibrosis and promotes regeneration in spiny mice (Acomys)

Although most mammals heal wounds with scar tissue, spiny mice (Acomys cahirinus) naturally regenerate skin and complex musculoskeletal tissues. The core signaling pathways driving mammalian tissue regeneration are poorly characterized. Here, we show that MAPK/ERK signaling acts as a major hub directing cellular injury responses towards regeneration. While immediate ERK activation was a shared feature of scarring (Mus musculus) and regenerating (Acomys) wounds, ERK activity was only sustained during regeneration. Upon ERK inhibition, the Acomys wound microenvironment exhibited key hallmarks of fibrosis, including a pro-scarring matrisome, epidermal differentiation and reduced proliferation. These findings indicate that ERK inhibition shifts tissue regeneration towards fibrosis. Conversely, the ectopic release of ERK activators (FGF/Neuregulin) in fibrotic scars, stimulated a pro-regenerative matrisome, cell proliferation and hair follicle neogenesis, thus promoting skin regeneration. Our data provide new insights into why some mammals regenerate better than others and open avenues to reverse fibrosis in favor of regeneration. TeaserFGF2 and NRG1 stimulate skin and hair follicle regeneration through ERK-mediated control of cell behavior in adult mammals.

cell biology↗

bioRxiv2021

Ischemic tolerance and cardiac repair in the African spiny mouse

Ischemic heart disease and by extension myocardial infarction is the primary cause of death worldwide, necessitating regenerative therapies to restore heart function. Current models of heart regeneration are restricted in that they are not of adult mammalian origin, precluding the study of class-specific traits that have emerged throughout evolution, and reducing translatability of research findings to humans. Here, we overcome those restrictions by introducing the African spiny mouse (Acomys spp.), a murid rodent that has recently been found to exhibit bona fide regeneration of the back skin and ear pinna. We show that spiny mice exhibit tolerance to myocardial infarction through superior survivability, improved ventricular conduction, smaller scar size, and near-absence of cardiac remodeling. Critically, spiny mice display increased vascularization and cardiomyocyte expansion, with an associated improvement in heart function. These findings present new avenues for mammalian heart research by leveraging unique tissue properties of the spiny mouse.

developmental biology↗

bioRxiv2020

Planarian CREB-binding protein (CBP) gene family regulates stem cell maintenance and differentiation

The regulation of stem cells plasticity and differentiation is still an open question in developmental biology. CBP (CREB-binding protein)/p300 is a conserved gene family which functions as a transcriptional co-activator and shows an important role in a wide range of cellular processes, such as cell death, DNA damage response and tumorigenesis. Moreover, CBPs have an acetyl transferase activity that is relevant as histone and non-histone acetylation results in changes in chromatin architecture and protein activity that affects gene expression. Many studies have shown the conserved functions of CBP/p300 on stem cell proliferation and differentiation. The planarian Schmidtea mediterranea is an excellent model to study in vivo the molecular mechanism underlying stem cell differentiation during regeneration. We have identified five different Smed-cbp genes in S. mediterranea that show different expression patterns. Functional analyses indicate that Smed-cbp-2 seems to be essential for stem cell maintenance and cell survival. On the other hand, the silencing of Smed-cbp-3 results in the growth of apparently normal blastemas; however, these remain largely depigmented and undifferentiated. Smed-cbp-3 silencing affects the differentiation of several cell lineages including neural, epidermal, digestive and excretory cell types. Finally, we have analyzed the predicted interactomes of CBP-2 and CBP-3 as an initial step to better understand their function on planarian stem cell biology.

developmental biology↗