Acetylated Signal Transducer and Activator of Transcription 3 Functions as Molecular Adaptor Independent of Transcriptional Activity during Human Cardiogenesis
Ashish Mehta et al., STEM CELLS
Signal transducer and activator of transcription 3 (STAT3) is regarded as a transcriptional activator of many target genes. In this study, we show that phosphorylated STAT3 and acetylated STAT3 are distinct isoforms, which function independently during cardiomyocyte (CM) formation. While phosphorylated STAT3 functions as the canonical transcriptional activator, acetylated STAT3 undergoes cleavage, generating a novel STAT3ζ fragment which functions as a molecular adaptor independent of transcriptional activity. This study for the first time demonstrates a novel molecular adaptor function of STAT3 that significantly enhances our understanding of the protein previously known to play a fundamental transcriptional activator roles across various cell types during mammalian development. This study not only enhances our understanding of signaling mechanisms governing human cardiogenesis but also brings a new paradigm to one of the most versatile molecules in mammalian biology, STAT3.
Feng Dong et al., STEM CELLS Translational Medicine
Stem cells therapy is a promising approach for the treatment of cardiovascular diseases. However, molecular pathways, mechanisms of action, and proper delivery systems are still to be optimized for clinical development. In this study, we analyzed the effect of mesenchymal stem cell secretome on cardiac recovery after acute myocardial infarction. We observed that overexpression of the protein kinase calcium/calmodulin-dependent protein kinase kinase-1 (CAMKK1) in either mesenchymal stem cells or upon direct injection of its encoding DNA into infarcted tissue results in improved cardiac function and increased vasculogenesis. Thus, CAMKK1 may be suitable as a therapeutic target for cardiac disease.
In Vivo Rescue of the Hematopoietic Niche by Pluripotent Stem Cell Complementation of Defective Osteoblast Compartments
Rhiannon Chubb et al., STEM CELLS
Given the central role of bone-forming osteoblasts in supporting bone marrow hematopoiesis and in maintaining bone mass and strength, osteoblasts represent an important target tissue for regenerative medicine. Although several groups have reported the directed differentiation of pluripotent stem cells (PSCs) into osteoblasts in vitro, the field has lacked a rigorous assay with which to evaluate the bone-forming and hematopoiesis-supporting capacity of PSC-derived osteoblasts in vivo. Here, we describe two novel complementation assays, with which we demonstrate that PSC-derived osteoblasts can compensate for the loss of osteoblast lineage cells in transgenic mice to form mineralized bone and bone marrow hematopoietic niche in vivo. Remarkably, the loss of >50% of endogenous osteoblasts during embryonic skeletal development can be rescued by the injected PSCs. These assays will greatly enhance the ability of researchers to evaluate the contribution of specific osteoblast lineage populations to skeletal development and hematopoiesis.
Agnes T. Reiner et al., STEM CELLS Translational Medicine
Extracellular vesicles (EVs) have been implicated as important and sometimes sufficient mediators of the effects of stem cells. Best-practice models must be developed for the rapid development of exosomes, microvesicles, and other EVs as therapeutic entities.
Video abstract from Dr. Cooke, et al. on his recently published STEM CELLS paper entitled, "Retinoic Acid Inducible Gene 1 Protein (RIG1)-like Receptor Pathway is Required for Efficient Nuclear Reprogramming." Read the paper here.
Video abstract from Drs. Cox, Hetz, Liao, Aertker, Ewing-Cobbs, Juranek, Savitz, Jackson, Romanowska-Pawliczek, Triolo, Dash, Pedroza, Lee, Worth, Aisiku, Choi, Holcomb, and Kitagawa on their recently published STEM CELLS paper entitled, "Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells." Read the paper here.Video Library