Mesenchymal stem cell-derived exosomes attenuate DNA damage response induced by cisplatin and bleomycin.

Stem cell-derived exosomes (SC-Exos) have been shown to protect cells from chemical-induced deoxyribonucleic acid (DNA) damage. However, there has been no systematic comparison of the efficacy of exosomes against different types of DNA damage. Therefore, in this study, we assessed the protective effect of exosomes derived from human embryonic stem cell-induced mesenchymal stem cells (hESC-MSC-Exos) on two types of DNA damage, namely, intra-/inter-strand crosslinks and DNA double-strand breaks induced by cisplatin (Pt) and bleomycin (BLM), respectively, in HeLa cells.

Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti.

Mammalian sensory hair cells (HCs) have limited capacity for regeneration, which leads to permanent hearing loss after HC death. Here, we used in vitro RNA-sequencing to show that the Hippo signaling pathway is involved in HC damage and self-repair processes. Turning off Hippo signaling through Mst1/2 inhibition or Yap overexpression induces YAP nuclear accumulation, especially in supporting cells, which induces supernumerary HC production and HC regeneration after injury.

Temporarily Epigenetic Repression in Bergmann Glia Regulates the Migration of Granule Cells.

Forming tight interaction with both Purkinje and granule cells (GCs), Bergmann glia (BG) are essential for cerebellar morphogenesis and neuronal homeostasis. However, how BG act in this process is unclear without comprehensive transcriptome landscape of BG. Here, high temporal-resolution investigation of transcriptomes with FACS-sorted BG revealed the dynamic expression of genes within given functions and pathways enabled BG to assist neural migration and construct neuron-glia network.

Nuclear import of Nkx2-2 is mediated by multiple pathways.

Nkx2-2 homeoprotein is essential for the development of the central nervous system and pancreas. Although the nuclear localization signals of Nkx2-2 have been identified, the responsible transport receptor is still unknown. Here, we demonstrate that imp α1 not only interacts with Nkx2-2 but also transports it into the nucleus in vitro by acting together with imp β1.

Nuclear import of aristaless-related homeobox protein via its NLS1 regulates its transcriptional function.

Nucleocytoplasmic transport of transcription factors is essential in eukaryotes. We previously reported the presence of two functional NLSs in the homeodomain protein, aristaless-related homeobox (Arx) protein, which is a key transcriptional repressor of LMO1, SHOX2, and PAX4 during development. NLS2, that overlaps the homeodomain, is recognized directly by multiple importin βs, but not by importin αs.

A novel role of proteasomal β1 subunit in tumorigenesis.

p27Kip1 is a key cell-cycle regulator whose level is primarily regulated by the ubiquitin-proteasome degradation pathway. Its β1 subunit is one of seven β subunits that form the β-ring of the 20S proteasome, which is responsible for degradation of ubiquitinated proteins. We report here that the β1 subunit is up-regulated in oesophageal cancer tissues and some ovarian cancer cell lines.

Karyopherins in nuclear transport of homeodomain proteins during development.

Homeodomain proteins are crucial transcription factors for cell differentiation, cell proliferation and organ development. Interestingly, their homeodomain signature structure is important for both their DNA-binding and their nucleocytoplasmic trafficking. The accurate nucleocytoplasmic distribution of these proteins is essential for their functions.