Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Directed reprogramming of human fibroblasts into fully differentiated neurons requires massive changes in epigenetic and transcriptional states. Induction of a chromatin environment permissive for acquiring neuronal subtype identity is therefore a major barrier to fate conversion. Here we show that the brain-enriched miRNAs miR-9/9 and miR-124 (miR-9/9-124) trigger reconfiguration of chromatin accessibility, DNA methylation, and mRNA expression to induce a default neuronal state. miR-9/9-124-induced neurons (miNs) are functionally excitable and uncommitted toward specific subtypes but possess open chromatin at neuronal subtype-specific loci, suggesting that such identity can be imparted by additional lineage-specific transcription factors. Consistently, we show that ISL1 and LHX3 selectively drive conversion to a highly homogeneous population of human spinal cord motor neurons. This study shows that modular synergism between miRNAs and neuronal subtype-specific transcription factors can drive lineage-specific neuronal reprogramming, providing a general platform for high-efficiency generation of distinct subtypes of human neurons.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679239 | PMC |
| http://dx.doi.org/10.1016/j.stem.2017.08.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Single-cell transcriptomic atlas of human retina from Chinese donors reveals population-specific cellular diversity.
Exp Eye Res
September 2025
Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo China, Ningbo, 315100, China. Electronic address:
The human retina exhibits complex cellular heterogeneity which is critical for visual function, yet comprehensive ethnic-specific references are scarce in ophthalmic transcriptomics. The lack of single-cell RNA sequencing (scRNA-seq) data from Asian populations particularly Chinese donors imposes significant limitations in understanding population-specific retinal biology. We constructed the first comprehensive single-cell transcriptomic atlas of the human retina from Chinese donors, generated through high-throughput scRNA-seq of ∼290,000 viable cells obtained from 18 fresh retinal specimens (living donor and post-mortem specimens).
View Article and Find Full Text PDFDesigning fluorescent estrogen mimetic 7-hydroxycoumarin probe substrates for human sulfotransferase enzymes.
Eur J Pharm Sci
August 2025
Institute of Biomedicine, Faculty of Medicine, University of Turku, FI-20014 University of Turku, Finland; InFLAMES Research Flagship Center, University of Turku, FI-20014 Turku, Finland.
Sulfonation is one of drug metabolism reactions affecting homeostasis of estrogens. C-3 aryl substituted 7-hydroxycoumarins are fluorescent estrogen mimetics; i.e.
View Article and Find Full Text PDFPrenatal stress induces transient developmental alterations in distinct GABAergic populations and leads to long-lasting behavioral abnormalities.
Neurobiol Stress
September 2025
Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.
Prenatal stress (PNS) is a well-established risk factor for psychiatric disorders, yet the underlying neurobiological mechanisms remain unclear. Here, we demonstrate that PNS induces long-term behavioral abnormalities, including increased anxiety- and depressive-like behaviors specifically in adult male mice. To investigate potential neurodevelopmental disruptions, we analyzed the medial prefrontal cortex (mPFC) at key postnatal stages.
View Article and Find Full Text PDFCharacteristic miRNA profiles represent clinicopathological diversity of small cell lung cancer.
J Pathol
August 2025
Department of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Small cell lung cancer (SCLC) is classified into distinct molecular subtypes based on the expression patterns of four transcription regulators: achaete-scute homolog 1 (ASCL1), neuronal differentiation 1 (NEUROD1), POU class 2 homeobox 3 (POU2F3), and yes-associated protein 1 (YAP1). MicroRNAs (miRNAs) play critical roles in cancer cellular processes but their subtype-specific implications in SCLC remain underexplored. Out of 46 surgically resected SCLC samples, miRNA visualization through in situ hybridization identified high expression of miR-375 in the ASCL1, NEUROD1, and ASCL1/NEUROD1 subtypes, and miR-9-5p in the POU2F3 subtype.
View Article and Find Full Text PDFMorphological variability may limit single-cell specificity to electric field stimulation.
Front Synaptic Neurosci
August 2025
Department of Physics, University of Ottawa, Ottawa, ON, Canada.
Introduction: Non-invasive brain stimulation techniques, widely used to manipulate neural excitability and behavior, are well studied at the meso- and macroscopic scales. However, less is known about their specificity at the level of individual cells.
Methods: Models based on real pyramidal and parvalbumin neuron morphologies created by the Allen Institute for Brain Science were characterized using metrics we devised to quantify various aspects of cellular morphology, ranging from whole cell attributes to net compartment length, branching, diameter and orientation.