Converting human skin cells to neurons: a new tool to study and treat brain disorders?

Recent publications in Cell Stem Cell (Son et?al., 2011; Ambasudhan et?al., 2011), PNAS (Pfisterer et?al., 2011), and Nature (Caiazzo et?al., 2011; Pang et?al., 2011; Yoo et?al., 2011) report that functional neurons can be directly generated from human fibroblast cells without going through the pluripotent state.     

iPSCs: induced back to controversy

Several recent reports (Mayshar et?al., 2010; Laurent et?al., 2011; Lister et?al., 2011; Gore et?al., 2011; Hussein et?al., 2011) uncover genetic and epigenetic alterations in induced pluripotent stem cells, stimulating debate about their future. However, will these important findings really impact what we hope to gain?     

Converted neural cells: induced to a cure?

Many neurodegenerative disorders such as Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and others often occur as a result of progressive loss of structure or function of neurons. Recently, many groups were able to generate neural cells, either differentiated from induced pluripotent stem cells (iPSCs) or converted from somatic cells. Advances in converted neural cells have opened a new era to ease applications for modeling diseases and screening drugs. In addition, the converted neural cells also hold the promise for cell replacement therapy (Kikuchi et al., 2011; Krencik et al., 2011; Kriks et al., 2011; Nori et al., 2011; Rhee et al., 2011; Schwartz et al., 2012). Here we will mainly discuss most recent progress on using converted functional neural cells to treat neurological diseases and highlight potential clinical challenges and future perspectives.     

Mechanisms involved in the neurotoxic and cognitive effects of developmental methamphetamine exposure

Methamphetamine exposure in utero leads to a variety of higher‐order cognitive deficits, such as decreased attention and working, and spatial memory impairments in exposed children (Piper et al., 2011; Roussotte et al., 2011; Kiblawi et al., 2011). As with other teratogens, the timing of methamphetamine exposure greatly determines its effects on both neuroanatomical and behavioral outcomes. Methamphetamine exposure in rodents during the third trimester human equivalent period of brain development results in distinct and long‐lasting route‐based and spatial navigation deficits (Williams et al., 2003; Vorhees et al., 2005, 2008, 2009;). Here, we examine the impact of neonatal methamphetamine‐induced neurotoxicity on behavioral outcomes, neurotransmission, receptor changes, plasticity proteins, and DNA damage. Birth Defects Research (Part C) 108:131–141, 2016. © 2016 Wiley Periodicals, Inc.     

Linking epithelial-mesenchymal transition to the well-known polarity protein Par6

Epithelial-mesenchymal transition (EMT) is involved in the formation of the body plan, tissue remodeling, and cancer progression. Two recent reports in Science (Barrios-Rodiles et al., 2005; Ozdamar et al., 2005) have decisively advanced our understanding of EMT. Par6 was identified as a key player in the control of tight junction (TJ) stability. This new study provides further insight into the protein networks involved in topologically regulated control of epithelial cell polarity and plasticity.     

Early human dispersals into the Iberian Peninsula: a comment on Martínez et al.(2010) and Garcia et al. (2011)

Garcia et al. (2011) recently discussed early human dispersals into the Iberian Peninsula, describing several putative lithic artifacts (Martínez et al., 2010) recovered from layer 7 of the Vallpara díssection (Madurell-Malapeira et al., 2010) in Terrassa (Vallès-Penedès Basin, Catalonia, Spain). According to the authors' opinion, such evidence (1) fills a gap in the chronology of early human occupation in Iberia, (2) indicates that these populations had primary and early access to carcasses, and (3) confirms that early human populations were equipped with advanced cultural traits enabling them to survive in unfavourable climatic conditions. We argue below that the record of human activity at Vallparadís (Martínez et al., 2010;Garcia et al., 2011) is doubtful and even that if confirmed, a chronological gap would remain (contra Garcia et al., 2011). Additional remarks on assertions by these authors on the Vallparadís geology, taphonomy and paleonvironment are also provided.     

Human rhinovirus C infection is associated with asthma in children determined by xTAG respiratory viral panel FAST

<正>Dear Editor,Cumulative evidence supports the role of early-life viral infections,especially respiratory syncytial virus(RSV)and human rhinovirus(HRV),as major antecedents of childhood asthma(Lemanske,2002;Jackson et al.,2008).In this study,the x TAG respiratory viral panel FAST(RVP FAST)assay,a multiplex polymerase chain reaction(PCR)-based method(Arens et al.,2010;BaladaLlasat et al.,2011;Gharabaghi et al.,2011;Selvaraju,2012),was used to investigate the association of infec-     

Evicting the pneumococcus from its nasopharyngeal lodgings

Adenylylation of Rab proteins appears to be an intriguing mechanism that Legionella pneumophila uses to modulate their activity during infection. Now the reverse reaction (deadenylylation) (Neunuebel et?al., 2011; Tan and Luo, 2011) and a new posttranslational modification (phosphocholination) of Rab1 (Mukherjee et?al., 2011) have been reported.     

Small RNAs loom large during reprogramming

In two independent Cell Stem Cell reports, the Morrisey and Mori groups show that human and mouse somatic cells can be reprogrammed to produce induced pluripotent stem cells by expressing microRNAs, completely eliminating the need for ectopic protein expression (Anokye-Danso et al., 2011; Miyoshi et al., 2011).     

Recombining DNA by protein swivels

Two new reports on serine recombinases, one of a crystal snapshot in an alternate rotational conformer poised for DNA cleavage (Keenholtz et al., 2011), and a second employing single-DNA molecule approaches (Bai et al., 2011), provide strong support for the subunit rotation model for exchanging DNA strands.     

Unveiled α-neurexins take center stage

Neurexins are presynaptic transmembrane proteins that play an essential role in synapse function. The crystal structures of α-neurexin extracellular domains (Chen et?al., 2011; Miller et?al., 2011) provide important insights into their conformational freedom and their putative spatial arrangement with binding partners in the synaptic cleft.     

Tales from the crypt: the expanding role of slow cycling intestinal stem cells

Similar to other highly self-renewing tissues, the intestinal epithelium contains both slowly and rapidly cycling progenitor/stem cells, though their relationship has been largely unexplored. Two recent reports in Nature (Tian et al., 2011) and Science (Takeda et al., 2011) shed new light on their dynamic interplay.     

Double take on Piwi protein/piRNA complex structure

Two recent studies by the Carlomagno/Pillai labs (Simon et?al., 2011) and the Patel group (Tian et?al., 2011) report the structures of complexes of Piwi PAZ domains with piRNA, utilizing two major methods in structural biology, NMR spectroscopy, and X-ray crystallography, and derive very similar structures with similar resolution.     

Moving right along: how PP1 helps clear the checkpoint

Spindle checkpoint silencing is crucial for cell-cycle progression, but mechanisms underlying this process remain mysterious. Two papers, one in this issue of Developmental Cell (Meadows et?al., 2011) and one in Current Biology (Rosenberg et?al., 2011), begin to show how phosphatase PP1-gamma connects chromosome-microtubule attachment with anaphase entry.     

A hormone sends instant messages to the genome

Accurate chromosome segregation during mitosis and meiosis is essential for cell viability. Two papers in this issue of Cell (Kitajima et al., 2011; Magidson et al., 2011) describe chromosome movements during cell division with unprecedented accuracy, revealing previously unrecognized features of chromosome spindle alignment and paving the way to quantitative phenotypic and mechanistic analyses of chromosome alignment during prometaphase.     

Testing the level of ant activity associated with quorum sensing: an empirical approach leading to the establishment and test of a null-model (response to the comment of Richardson et al.)

In a paper in this journal (Nouvellet et al., 2010), we presented results from experiments on the behaviour of the Pharaoh's ant, Monomorium pharaonis, along with a substantial statistical and theoretical analysis of the results. In a minor part of our paper, we compared our results with the related work of Richardson et al. (2010a). These authors have subsequently commented on our interpretation of their work (Richardson et al., 2011). In this Letter we respond to the comments of Richardson et al. (2011), and give detailed arguments why we stand by our original conclusions.     

Gene editing in stem cells hits the target

Two recent reports describe promising, highly efficient methods to modify genes in pluripotent stem cells using zinc finger nuclease (ZFN)-mediated (Soldner et?al., 2011) or helper-dependent adenovirus (HDAdV)-mediated (Liu et?al., 2011b) gene modification. These technical developments will have far ranging effects on the rapidly growing field of regenerative medicine.     

Breaking the cell cycle of HSCs by p57 and friends

The cell cycle regulators involved in maintaining the quiescence, and thereby the self-renewal capacity, of somatic stem cells have long been elusive. Two new Cell Stem Cell articles in this issue (Matsumoto et?al., 2011; Zou et?al., 2011) now show that the CDK inhibitor p57 is a crucial brake for cycling HSCs, and links self-renewal activity to cell cycle quiescence.     

Roles of Tet2 in meiosis,fertility and reproductive aging

Dear Editor, Ten-eleven translocation(Tet)enzymes play important roles in DNA demethylation involved in various biological pro-cesses including stem cell pluripotency and differentiation,and tumorigenesis(Dawlaty et al.,2013;Wu and Zhang,2017).Tet2 deficiency or mutation leads to severe hematopoietic defects or myeloid malignancies in mice(Delhommeau et al.,2009;Ko et al.,2010;Moran-Crusio et al.,2011).Restoration of TET2 blocks aberrant self-re-newal and leukemia progression in patients possessing TET2 mutations(Cimmino et al.,2017).DNA methylation-based biomarkers,or"epigenetic clocks",link developmental and maintenance processes to biological aging(Horvath and Raj,2018).Interestingly,age-associated TET2 mutations have been found to drive myeloid dysfunction,cancer and cardiovascular disease(review(Ferrone et al.,2020)).Nevertheless,there has been lack of direct evidence demonstrating that Tet2 mutations or deficiency can actually accelerate aging.