The progress in optic nerve regeneration, where are we?

Optic nerve regeneration is an important area of research. It can be used to treat patients suffering from optic neuropathy and provides insights into the treatment of numerous neurodegenerative diseases. There are many hurdles impeding optic regeneration in mammals. The mammalian central nervous system is non-permissive to regeneration and intrinsically lacks the capacity for axonal regrowth. Any axonal injury also triggers a vicious cycle of apoptosis. Understanding these hurdles provides us with a rough framework to appreciate the essential steps to bring about optic nerve regeneration： enhancing neuronal survival, axon regeneration, remyelination and establishing functional synapses to the original neuronal targets. In this review article, we will go through current potential treatments for optic nerve regeneration, which includes neurotrophic factor provision, inflammatory stimulation, growth inhibition suppression, intracellular signaling modification and modeling of bridging substrates.

High-resolution two-photon transcranial imaging of brain using direct wavefront sensing

Imaging of the brain in its native state at high spatial resolution poses major challenges to visualization techniques.Two-photon microscopy integrated with the thinned-skull or optical clearing skull technique provides a minimally invasive tool for in vivo imaging of the cortex of mice without activating immune response and inducing brain injury.However,the imaging contrast and spatial resolution are severely compromised by the optical heterogeneity of the skull,limiting the imaging depth to the superficial layer.In this work,an optimized configuration of an adaptive optics two-photon microscope system and an improved wavefront sensing algorithm are proposed for accurate correction for the aberrations induced by the skull window and brain tissue.Using this system,we achieved subcellular resolution transcranial imaging of layer 5 pyramidal neurons up to 700μm below pia in living mice.In addition,we investigated microglia–plaque interaction in living brain of Alzheimer’s disease and demonstrated high-precision laser dendrotomy and single-spine ablation.

Cebpa is essential for the embryonic myeloid progenitor and neutrophil maintenance in zebrafish

In vertebrates, myeloid cells arise from multiple waves of development： the first or embryonic wave of myelopoiesis initiates early from non-hematopoietic stem cell（HSC） precursors and gives rise to myeloid cells transiently during early development; whereas the second or adult wave of myelopoiesis emerges later from HSCs and produces myeloid cells continually during fetal and adult life. In the past decades, a great deal has been learnt about the development of myeloid cells from adult myelopoiesis, yet the genetic network governing embryonic myelopoiesis remains poorly defined. In this report, we present an in vivo study to delineate the role of Cebpa during zebrafish embryonic myelopoiesis. We show that embryonic myelopoiesis in cebpa-deficient zebrafish mutants initiates properly but fails to produce macrophages and neutrophils. The lack of macrophages and neutrophils in the mutants is largely attributed to the cell cycle arrest of embryonic myeloid progenitors, resulting in the impairment of their maintenance and subsequent differentiation. We further show that Cebpa, perhaps acting cooperatively with Runx1, plays a critical role in embryonic neutrophil maintenance. Our findings reveal a new role of Cebpa in embryonic myelopoiesis.

Nlrc3-like is required for microglia maintenance in zebrafish

Microglia are tissue-resident macrophages residing in the central nervous system (CNS) and play critical roles in removing cellular debris and infectious agents as well as regulating neurogenesis and neuronal activities. Yet, the molecular basis underlying the establishment of microglia pool and the maintenance of their homeostasis in the CNS remain largely undefined. Here we report the identification and characterization of a mutant zebrafish, which harbors a point mutation in the nucleotide-binding oligomerization domain (NOD) like receptor gene nlrc3-like, resulting in the loss of microglia in a temperature sensitive manner. Temperature shift assay reveals that the late onset of nlrc3-like deficiency leads to excessive microglia cell death. Further analysis shows that the excessive microglia death in nlrc3-like deficient mutants is attributed, at least in part, to aberrant activation of canonical inflammasome pathway. Our study indicates that proper regulation of inflammasome cascade is critical for the maintenance of microglia homeostasis.

CELLO:a longitudinal data analysis toolbox untangling cancer evolution

The complex pattern of cancer evolution poses a huge challenge to precision oncology.Longitudinal sequencing of tumor samples allows us to monitor the dynamics of mutations that occurred during this clonal evolution process.Here,we present a versatile toolbox,namely CELLO(Cancer EvoLution for Longitudinal data),accompanied with a step-by-step tutorial,to exemplify how to profile,analyze and visualize the dynamic change of somatic mutational landscape using longitudinal genomic sequencing data.Moreover,we customize the hypermutation detection module in CELLO to adapt targeted-DNA and whole-transcriptome sequencing data,and verify the extensive applicability of CELLO in published longitudinal datasets from brain,bladder and breast cancers.The entire tutorial and reusable programs in MATLAB,R and docker versions are open access at https://github.com/WaiigLabHKUST/CELLO.

Tissue-resident macrophages: from zebrafish to mouse

Tissue-resident macrophages(TRMs),generally found in tissues under normal physiological conditions,play crucial roles not only in immunity but also in tissue development and homeostasis.Because of their diverse functions,dysregulation of their development and function has been implicated in many human disorders.In the past decade,a great deal of extensive studies have been conducted in various model organisms with cutting-edge technologies to explore the origin and function of TRMs.In this review,we summarize the recent findings on TRMs in mouse and zebrafish and compare the similarity/differences between these two species.