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Corrigendum: Patch-Seq Protocol to Analyze the Electrophysiology, Morphology and Transcriptome of Whole Single Neurons Derived From Human Pluripotent Stem Cells.

Frontiers in molecular neuroscience · 2019 · 12: 150

[This corrects the article DOI: 10.3389/fnmol.2018.00261.].

PMID 31244603 DOI ↗

The RNA Helicase DDX6 Controls Cellular Plasticity by Modulating P-Body Homeostasis.

Cell stem cell · 2019 · 25(5): 622-638.e13

Post-transcriptional mechanisms have the potential to influence complex changes in gene expression, yet their role in cell fate transitions remains largely unexplored. Here, we show that suppression of the RNA helicase DDX6 endows human and mouse primed embryonic stem cells …

PMID 31588046 DOI ↗

Peptide Brush Polymers for Efficient Delivery of a Gene Editing Protein to Stem Cells.

Angewandte Chemie (International ed. in English) · 2019 · 58(44): 15646-15649

The scarcity of effective means to deliver functional proteins to living cells is a central problem in biotechnology and medicine. Herein, we report the efficient delivery of an active DNA-modifying enzyme to human stem cells through high-density cell penetrating peptide …

PMID 31404473 DOI ↗

Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development.

Cell stem cell · 2019 · 25(4): 558-569.e7

Structural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. …

PMID 31474560 DOI ↗

Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson's Disease.

Cell stem cell · 2019 · 24(6): 1006

PMID 31173705 DOI ↗

Patch-Seq Protocol to Analyze the Electrophysiology, Morphology and Transcriptome of Whole Single Neurons Derived From Human Pluripotent Stem Cells.

Frontiers in molecular neuroscience · 2018 · 11: 261

The human brain is composed of a complex assembly of about 171 billion heterogeneous cellular units (86 billion neurons and 85 billion non-neuronal glia cells). A comprehensive description of brain cells is necessary to understand the nervous system in health …

PMID 30147644 DOI ↗

Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.

Acta neuropathologica · 2018 · 136(3): 405-423

Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched …

PMID 29881994 DOI ↗

Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson's Disease.

Cell stem cell · 2018 · 23(1): 123-131.e6

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of midbrain neurons (MBNs). Recent evidence suggests contribution of the adaptive immune system in PD. Here, we show a role for human T lymphocytes as cell death inducers …

PMID 29979986 DOI ↗

Single-Cell Alternative Splicing Analysis with Expedition Reveals Splicing Dynamics during Neuron Differentiation.

Molecular cell · 2017 · 67(1): 148-161.e5

Alternative splicing (AS) generates isoform diversity for cellular identity and homeostasis in multicellular life. Although AS variation has been observed among single cells, little is known about the biological or evolutionary significance of such variation. We developed Expedition, a computational …

PMID 28673540 DOI ↗

iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

Stem cell reports · 2017 · 8(4): 1086-1100

Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 …

PMID 28410642 DOI ↗

High-Throughput and Cost-Effective Characterization of Induced Pluripotent Stem Cells.

Stem cell reports · 2017 · 8(4): 1101-1111

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) offers the possibility of studying the molecular mechanisms underlying human diseases in cell types difficult to extract from living patients, such as neurons and cardiomyocytes. To date, studies have been published …

PMID 28410643 DOI ↗

Predicting the functional states of human iPSC-derived neurons with single-cell RNA-seq and electrophysiology.

Molecular psychiatry · 2016 · 21(11): 1573-1588

Human neural progenitors derived from pluripotent stem cells develop into electrophysiologically active neurons at heterogeneous rates, which can confound disease-relevant discoveries in neurology and psychiatry. By combining patch clamping, morphological and transcriptome analysis on single-human neurons in vitro, we defined …

PMID 27698428 DOI ↗

Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.

Neuron · 2016 · 92(4): 780-795

HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role …

PMID 27773581 DOI ↗

The Calcineurin Variant CnAβ1 Controls Mouse Embryonic Stem Cell Differentiation by Directing mTORC2 Membrane Localization and Activation.

Cell chemical biology · 2016 · 23(11): 1372-1382

Embryonic stem cells (ESC) have the potential to generate all the cell lineages that form the body. However, the molecular mechanisms underlying ESC differentiation and especially the role of alternative splicing in this process remain poorly understood. Here, we show …

PMID 27746127 DOI ↗

Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model.

Genome medicine · 2016 · 8(1): 94

Tuberous sclerosis complex (TSC) is a genetic disease characterized by benign tumor growths in multiple organs and neurological symptoms induced by mTOR hyperfunction. Because the molecular pathology is highly complex and the etiology poorly understood, we employed a defined human …

PMID 27655340 DOI ↗

Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.

Nature communications · 2016 · 7: 12143

The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs …

PMID 27378374 DOI ↗

Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells.

Nature · 2016 · 532(7600): 508-511

Umbilical cord blood-derived haematopoietic stem cells (HSCs) are essential for many life-saving regenerative therapies. However, despite their advantages for transplantation, their clinical use is restricted because HSCs in cord blood are found only in small numbers. Small molecules that enhance …

PMID 27121842 DOI ↗

Enhanced CLIP Uncovers IMP Protein-RNA Targets in Human Pluripotent Stem Cells Important for Cell Adhesion and Survival.

Cell reports · 2016 · 15(3): 666-679

Human pluripotent stem cells (hPSCs) require precise control of post-transcriptional RNA networks to maintain proliferation and survival. Using enhanced UV crosslinking and immunoprecipitation (eCLIP), we identify RNA targets of the IMP/IGF2BP family of RNA-binding proteins in hPSCs. At the broad …

PMID 27068461 DOI ↗

PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically.

Nature medicine · 2016 · 22(1): 37-45

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene, which encodes a polyglutamine tract in the HTT protein. We found that peroxisome proliferator-activated receptor delta (PPAR-δ) interacts with HTT …

PMID 26642438 DOI ↗

Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.

Circulation · 2015 · 131(14): 1278-1290

Long noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators with important functions in development and disease. Here, we sought to identify and functionally characterize novel lncRNAs critical for vertebrate development. By relying on human pluripotent stem cell differentiation models, …

PMID 25739401 DOI ↗

Human cytomegalovirus infection of human embryonic stem cell-derived primitive neural stem cells is restricted at several steps but leads to the persistence of viral DNA.

Journal of virology · 2014 · 88(8): 4021-39

Congenital human cytomegalovirus (HCMV) infection is a major cause of central nervous system structural anomalies and sensory impairments. It is likely that the stage of fetal development, as well as the state of differentiation of susceptible cells at the time …

PMID 24453373 DOI ↗

Differential L1 regulation in pluripotent stem cells of humans and apes.

Nature · 2013 · 503(7477): 525-529

Identifying cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic understanding of the evolution and diversity of our own species. Until now, preserved tissues have been the main source for most comparative studies between …

PMID 24153179 DOI ↗

Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment.

Genes & development · 2013 · 27(21): 2332-44

A critical but molecularly uncharacterized step in heart formation and regeneration is the process that commits progenitor cells to differentiate into cardiomyocytes. Here, we show that the endoderm-derived dual Nodal/bone morphogenetic protein (BMP) antagonist Cerberus-1 (Cer1) in embryonic stem cell …

PMID 24186978 DOI ↗

Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs.

Nature neuroscience · 2012 · 15(11): 1488-97

FUS/TLS (fused in sarcoma/translocated in liposarcoma) and TDP-43 are integrally involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We found that FUS/TLS binds to RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU-binding motif. We …

PMID 23023293 DOI ↗

LIN28 binds messenger RNAs at GGAGA motifs and regulates splicing factor abundance.

Molecular cell · 2012 · 48(2): 195-206

LIN28 is a conserved RNA-binding protein implicated in pluripotency, reprogramming, and oncogenesis. It was previously shown to act primarily by blocking let-7 microRNA (miRNA) biogenesis, but here we elucidate distinct roles of LIN28 regulation via its direct messenger RNA (mRNA) …

PMID 22959275 DOI ↗