Fundacion

Publicado en: Nature Communications

Abstract. Short-term, systemic expression of the Yamanaka reprogramming factors (Oct-3/4, Sox2, Klf4 and c-Myc [OSKM]) has been shown to rejuvenate aging cells and promote tissue regeneration in vivo. However, the mechanisms by which OSKM promotes tissue regeneration are unknown. In this work, we focus on a specific tissue and demonstrate that local expression of OSKM, specifically in myofibers, induces the activation of muscle stem cells or satellite cells (SCs), which accelerates muscle regeneration in young mice. In contrast, expressing OSKM directly in SCs does not improve muscle regeneration. Mechanistically, expressing OSKM in myofibers regulates the expression of genes important for the SC microenvironment, including upregulation of p21, which in turn downregulates Wnt4. This is critical because Wnt4 is secreted by myofibers to maintain SC quiescence. Thus, short-term induction of the Yamanaka factors in myofibers may promote tissue regeneration by modifying the stem cell niche.

Referencia:

Chao Wang, Ruben Rabadan Ros, Paloma Martinez-Redondo, Zaijun Ma, Lei Shi, Yuan Xue, Isabel Guillen-Guillen, Ling Huang, Tomoaki Hishida, Hsin-Kai Liao, Estrella Nuñez Delicado, Concepcion Rodriguez Esteban, Pedro Guillen-Garcia, Pradeep Reddy & Juan Carlos Izpisua Belmonte

Link: https://doi.org/10.1038/s41467-021-23353-z

Publicado en: Protein Cell

Martinez-Redondo, P., Guillen-Guillen, I., Davidsohn, N. et al. αKLOTHO and sTGFβR2 treatment counteract the osteoarthritic phenotype developed in a rat model. Protein Cell

Homeostasis and repair are critical biological processes that allow for tissue and organ preservation and function in multi-cellular organisms. Their regulation and extension vary drastically across the animal kingdom, and mammals show limited tissue-specific regenerative capacity that declines with age. During aging, articular cartilage is one of the tissues that undergo substantial changes in the matrix structure, molecular composition, metabolic activity, and mechanical properties (Loeser et al. 2016). As a result, articular cartilage experiences impaired homeostasis and limited capacity to undergo repair, contributing to osteoarthritis (OA) development (Loeser et al. 2016). OA is the most prevalent musculoskeletal disorder among the elderly and is the leading cause of disability in the US due to pain associated with the disease (Zhang et al. 2016). Although symptomatic pain relief is possible (Zhang et al. 2016), treatments to cure the pathology are currently unavailable. Interestingly, contrary to the loss of homeostasis and repair capacity with age, during embryogenesis as well as a short period after birth, mammals seem to have a higher regeneration capacity (Vivien et al. 2016). These and other facts beg the question of whether therapeutic targets can be developed towards the enhancement of the low regenerative capacity observed during adulthood and worsen upon aging.

Referencia:

Paloma Martinez-Redondo, Isabel Guillen-Guillen, Chao Wang, Javier Prieto, Masakazu Kurita, Fumiyuki Hatanaka, Cuiqing Zhong, Reyna Hernandez-Benitez, Tomoaki Hishida, Takashi Lezaki, Akihisa Sakamoto, Amy N. Nemeth, Yuriko Hishida, Concepcion Rodriguez Esteban, Kensaku Shojima, Pradeep Reddy & Juan Carlos Izpisua Belmonte

Paloma Martinez-Redondo and Isabel Guillen-Guillen have contributed equally to this work.

Link: https://link.springer.com/article/10.1007%2Fs13238-019-00685-7