Abstract: Here we show that epigenetic control of Neuregulin-1 (NRG1) affects adipose differentiation of stem cells in vitro. Building on this finding, we established a model in which NRG1 is a white adipose tissue (WAT) specific regulator analogous to the role of NRG4 in black adipose tissue (BAT). In this light, NRG1 functions in a paracrine or autocrine manner to regulate formation of new adipocytes from stem populations, both in vitro and in vivo. In neurons, NRG1 has been shown already to play a similar role, promoting neuronal cell differentiation from progenitors in the vertebrate cortex and retina and even promoting neuronal differentiation in vitro. Similarly, in the heart, NRG1 promotes differentiation of cardiomyocytes from their stem cell progenitors both in vivo and in vitro and for this reason has been successfully tested in clinical trials for heart failure.

Abstract: Compositions of the present disclosure include a first dCas9-FokI-sgRNA complex and a second dCas9-FokI-sgRNA complex. The first sgRNA is configured to target a first side of a genomic fusion site and the second sgRNA is configured to target a second side of the genomic fusion site. The first and second complexes only cut DNA upon dimerization. Thus, upon binding of both first dCas9-FokI-sgRNA complex and second dCas9-FokI-sgRNA complex, the dimer is produced and DNA cleavage proceeds at the genomic fusion site. The dCas9-FokI-sgRNA complexes are loaded on a folded-DNA shell for transport across the cellular membrane. The shell has a viral-mimic structure that maximizes cell entry, is non-cytotoxic, has low-to-nonimmunogenicity, and provides excellent capacity to enclose and protect the complexes. These systems exhibit both cellular (via the shell) and molecular (via the complexes) specificity, significantly reducing off-target activity and the associated harmful side-effects.

Abstract: Here we show that epigenetic control of Neuregulin-1 (NRG1) affects adipose differentiation of stem cells in vitro. Building on this finding, we established a model in which NRG1 is a white adipose tissue (WAT) specific regulator analogous to the role of NRG4 in black adipose tissue (BAT). In this light, NRG1 functions in a paracrine or autocrine manner to regulate formation of new adipocytes from stem populations, both in vitro and in vivo. In neurons, NRG1 has been shown already to play a similar role, promoting neuronal cell differentiation from progenitors in the vertebrate cortex and retina and even promoting neuronal differentiation in vitro. Similarly, in the heart, NRG1 promotes differentiation of cardiomyocytes from their stem cell progenitors both in vivo and in vitro and for this reason has been successfully tested in clinical trials for heart failure.