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Human pluripotent stem cell derived neurons have the potential for cell replacement therapy for brain injury and disease but problems on transplantation need to be overcome. Here, the authors use a microtopographic scaffold to graft neurons into both hippocampal organoids and the mouse brain striatum.

Dystrophic Epidermolysis Bullosa is an uncurable monogenetic skin disease. Here, Neumayer et al. develop a cGMP-compatible CRISPR- and iPS cell-based approach that produces gene-corrected, autologous skin composite grafts for definitive treatment.

The neuron-specific transcription factor Myt1l represses many somatic lineage programs, but not the neuronal lineage program, to both induce and maintain neuronal identity.

Identification of transient early induced pluripotency reprogramming intermediates allows for mechanistic insight into the reprogramming process.

This study reports the structural characterization of C1q-like protein 3 (C1ql3) with adhesion-GPCR brain-specific angiogenesis inhibitor-3 (BAI3).

Hematopoietic cell transplantation (HCT) may be a promising therapy for treatment-refractory multiple sclerosis (MS). Mader et al. Describe beneficial effects of autologous HCT in a mouse model of MS and identify a myeloid transcriptional signature associated with neuroprotection.

Generating induced pluripotent stem (iPS) cells is still an inefficient process, in part because the delivery of reprogramming factors by retroviral vectors yields cell populations that are genetically heterogeneous. Wernig et al. increase efficiency by producing iPS-cell chimeric mice from which they isolate cells bearing identical proviral insertions that support drug-inducible reprogramming.

Chou et al. generate transdifferentiated human neurons from fibroblasts from young or aged individuals and patients with Alzheimer’s disease. Studies of endolysosomes and proteostasis suggest a role for lysosomal quality control in Alzheimer’s disease pathology.

Two groups derived neural and mesodermal cells from human fibroblasts by going through a partially reprogrammed intermediate.

Global transcription factor activity is measured by screening cell extracts with an oligonucleotide library.

The transcriptome changes driving the conversion of fibroblasts to neurons at the single-cell level are reported, revealing that early neuronal reprogramming steps are homogenous, driven by the proneural pioneer factor Ascl1; the expression of myogenic genes then has a dampening effect on efficiency, which needs to be counteracted by the neuronal factors Myt1l and Brn2 for more efficient reprogramming.

Mabe et al. find that GD2 levels correlate with lineage plasticity in neuroblastoma and identify ST8SIA1 as the key enzyme in GD2 synthesis. EZH2 inhibition in mesenchymal neuroblastoma cells elevates ST8SIA1, synergizing with anti-GD2 antibodies.

Lee, Mall et al. explore why the sequence-related transcription factors Myod1 and Ascl1 lead to different reprogramming outcomes when expressed in fibroblasts, despite binding similar targets.

We present a protocol for generating mouse ESC-derived induced neuronal cells via lentiviral Tet-On inducible expression of NGN2 for the direct comparison of human and mouse neuronal populations.

The E3 ligase SIFI is identified as a dedicated silencing factor of the integrated stress response, a finding that has implications for the development of therapeutics for neurodegenerative diseases caused by mitochondrial protein import stress.

Four transcription factors Oct4, Sox2, c-Myc and Klf4 are known to convert fibroblasts to pluripotent stem cells, if Fbx15 expression is also selected. But the induced stem cells were shown to be distinct from normal embryonic stem cells. However, if cells expressing Nanog and Oct4 are selected, then the reprogrammed fibroblasts are similar to embryonic stem cells in both biological potency and epigenetic state.

Epigenomic profiling and massively parallel reporter assays identify 892 functional differentially-active single-nucleotide variants (daSNVs) linked to ten neuropsychiatric diseases. CRISPRi and gene editing approaches show magnesium transport dysfunction as a common genetic pathomechanism.

Expression of transcription factors can convert one cell type to another beyond developmental paths. Here, the authors show that cells can take two mechanistically distinct paths in the same transition paradigm when driven by the similar proneural factors Ascl1 and Ngn2.

Two studies show direct conversion of mouse embryonic fibroblasts to oligodendrocyte progenitor cells capable of generating myelinating oligodendrocytes.

Mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. Here, mature differentiated cells are directed, via a combination of a few transcription factors (distinct from those described for generating iPS cells), to form functional neurons in vitro, without having to revert the fibroblasts to an embryonic state.

Transient transcription factor expression rapidly induces a homogenous population of mature GABAergic neurons from human pluripotent stem cells, aiding the study of inhibitory neuron function and disease.

Endocytosis and degradation of plasma membrane proteins in the axon initial segment, together with the diffusion-barrier mechanism, maintain a polarized distribution of plasma membrane proteins in Caenorhabditis elegans, mouse, rat and human neurons.

Fibroblasts from old mice are heterogeneous, which affects the ability of these fibroblasts to reprogram into induced pluripotent stem cells in vitro and influences wound healing rate in vivo.

A genomic analysis of the reprogramming of murine fibroblasts and B lymphocytes was performed. It is shown that fully reprogrammed cells display gene expression and epigenetic states that are highly similar to embryonic stem cells. But in stable partially reprogrammed cell lines, there is reactivation of a distinct subset of stem cell-related genes and incomplete repression of lineage-specifying transcription factors.

Single-molecule-based sequencing technology is applied to generate genome-wide maps of chromatin modifications in mammalian cells. Histone marks can discriminate genes that are active, poised for activation, or stably repressed and therefore reflect cell state and developmental potential.

In vivo reprogramming of astrocytes to dopamine neurons improves motor behavior in a mouse model of Parkinson's disease.

RNA interference screens were used to identify chromatin-associated factors that impede reprogramming of somatic cells into iPS cells; suppression of the chromatin assembly factor CAF-1 enhances the generation of iPS cells by rendering chromatin more accessible to pluripotency transcription factors.

Zhang et al. design optogenetically controlled artificial transport vehicles that can be activated reversibly to manipulate cargo transport, impede neurite development and functionally characterize filopodial networks in axolotls.

Genome-scale DNA methylation profiles have been generated at nucleotide resolution in mammalian cells using a combination of high-throughput bisulphite sequencing and single molecule-based sequencing. The DNA methylation maps cover the vast majority of CpG islands, as well as several other genomic regions, in murine embryonic stem cells, cells derived from ES cells and various primary cells.

In response to the need for a defined set of criteria to assess stem-cell potency, this review proposes guidelines for the evaluation of newly derived pluripotent stem cells, from functional assays to integrative molecular analyses of transcriptional, epigenetic and metabolic states.