A5022300313- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- Renal and related cancers
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Genomics and Chromatin Dynamics
- Neuroinflammation and Neurodegeneration Mechanisms
- Viral Infections and Outbreaks Research
- Neuroscience and Neural Engineering
- Photoreceptor and optogenetics research
- Gene expression and cancer classification
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Congenital heart defects research
- dental development and anomalies
- Environmental DNA in Biodiversity Studies
- Cancer Genomics and Diagnostics
- Zebrafish Biomedical Research Applications
- Developmental Biology and Gene Regulation
- Hepatitis B Virus Studies
- Cancer Cells and Metastasis
- Liver physiology and pathology
- Neural dynamics and brain function
- Forensic and Genetic Research
Stanford University
2022-2024
Organogenesis (United States)
2022-2023
Neurosciences Institute
2023
Max Planck Institute for Evolutionary Anthropology
2015-2021
Helmholtz Centre for Environmental Research
2017
Martin Luther University Halle-Wittenberg
2017
German Centre for Integrative Biodiversity Research
2017
Leipzig University
2014-2016
Cerebral organoids-3D cultures of human cerebral tissue derived from pluripotent stem cells-have emerged as models cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) dissect compare composition progenitor-to-neuron lineage relationships organoids fetal neocortex. Covariation network analysis using...
Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans. This is thought primarily reflect differences in proliferation versus differentiation neural progenitors during cortical development. Here, we have searched for such by analysing cerebral organoids from human and chimpanzees using immunohistofluorescence, live imaging, single-cell transcriptomics. We find that cytoarchitecture, cell type composition, neurogenic gene expression programs humans are...
Identification of gene expression traits unique to the human brain sheds light on molecular mechanisms underlying evolution. Here, we searched for uniquely by analyzing 422 samples from humans, chimpanzees, bonobos, and macaques representing 33 anatomical regions, as well 88,047 cell nuclei composing three these regions. Among cerebral cortex areas, hypothalamus, cerebellar gray white matter evolved rapidly in humans. At cellular level, astrocytes oligodendrocyte progenitors displayed more...
ABSTRACT Deconstructing and then reconstructing developmental processes ex vivo is crucial to understanding how organs assemble physiology can be disrupted in disease. Human 3D stem cell-derived systems, such as organoids, have facilitated this pursuit; however, they often do not capture inter-tissue or inter-lineage cellular interactions that give rise emergent tissue properties during development. Assembloids are self-organizing systems result from the integration of multiple organoids...
We generated induced excitatory neurons (iNeurons, iNs) from chimpanzee, bonobo, and human stem cells by expressing the transcription factor neurogenin-2 (NGN2). Single-cell RNA sequencing showed that genes involved in dendrite synapse development are expressed earlier during iNs maturation chimpanzee bonobo than cells. In accordance, first 2 weeks of differentiation, repetitive action potentials more spontaneous activity iNs, extended neurites higher total length. However, axons were...
Abstract The unprecedented outbreak of Ebola in West Africa resulted over 28,000 cases and 11,000 deaths, underlining the need for a better understanding biology this highly pathogenic virus to develop specific counter strategies. Two filoviruses, Marburg viruses, result severe often fatal infection humans. However, bats are natural hosts survive filovirus infections without obvious symptoms. molecular basis striking difference response is not well understood. We report systematic overview...
Patterning of the neural tube establishes midbrain and hindbrain structures that coordinate motor movement, process sensory input, integrate cognitive functions. Cellular impairment within these underlie diverse neurological disorders, in vitro organoid models promise inroads to understand development, model disease, assess therapeutics. Here, we use paired single-cell transcriptome accessible chromatin sequencing map cell composition regulatory mechanisms hindbrain. We find existing...
Organoids and assembloids have emerged as a promising platform to model aspects of nervous system development. Longterm, minimally-invasive recordings in these multi-cellular systems are essential for developing disease models. Current technologies, such patch-clamp, penetrating microelectrodes, planar electrode arrays substrate-attached flexible electrodes, do not, however, allow chronic recording organoids suspension, which is necessary preserve their architecture. Inspired by the art...
Induced pluripotent stem cells (iPSCs) from diverse humans offer the potential to study human functional variation in controlled culture environments. A portion of this originates an ancient admixture between modern and Neandertals, which introduced alleles that left a phenotypic legacy on individual today. Here, we show large iPSC repository harbors extensive Neandertal DNA, including contribute phenotypes diseases, encode hundreds amino acid changes, alter gene expression specific tissues....
ABSTRACT The human brain has changed dramatically since humans diverged from our closest living relatives, chimpanzees and the other great apes 1–5 . However, genetic developmental programs underlying this divergence are not fully understood 6–8 Here, we have analyzed stem cell-derived cerebral organoids using single-cell transcriptomics (scRNA-seq) accessible chromatin profiling (scATAC-seq) to explore gene regulatory changes that specific humans. We first analyze cell composition...
ABSTRACT Identification of gene expression traits unique to the human brain sheds light on mechanisms cognition. Here we searched for separating humans from other primates by analyzing 88,047 cell nuclei and 422 tissue samples representing 33 regions humans, chimpanzees, bonobos, macaques. We show that evolves rapidly within types, with more than two-thirds type-specific differences not detected using conventional RNA sequencing samples. Neurons tend evolve faster in all hominids, but...