scholarly journals Somatic mosaicism in the mature brain reveals clonal cellular distributions during cortical development

Author(s):  
Martin W. Breuss ◽  
Xiaoxu Yang ◽  
Danny Antaki ◽  
Johannes C. M. Schlachetzki ◽  
Addison J. Lana ◽  
...  

AbstractThe structure of the human neocortex underlies species-specific features and is a reflection of intricate developmental programs. Here we analyzed neocortical cellular lineages through a comprehensive assessment of brain somatic mosaicism—which acts as a neutral recorder of lineage history. We employed deep whole genome and variant sequencing in a single postmortem neurotypical human brain across 25 anatomic regions and three distinct modalities: bulk geographies, sorted cell types, and single nuclei. We identified 259 mosaic variants, revealing remarkable differences in localization, clonal abundance, cell type specificity, and clade distribution. We identified a set of hierarchical cellular diffusion barriers, whereby the left-right axis separation of the neocortex occurs prior to anterior-posterior and dorsal-ventral axis separation. We also found that stochastic distribution is a driver of clonal dispersion, and that rules regarding cellular lineages and anatomical boundaries are often ignored. Our data provides a comprehensive analysis of brain somatic mosaicism across the human cerebral cortex, deconvolving clonal distributions and migration patterns in the human embryo.One Sentence SummaryComprehensive evaluation of brain somatic mosaicism in the adult human identifies rules governing cellular distribution during embryogenesis.

2020 ◽  
Vol 27 (1) ◽  
pp. 56-63
Author(s):  
Jong-Gil Park ◽  
Chang-uk Park ◽  
Kyoung-Soon Jin ◽  
Yang-Mo Kim ◽  
Hee-Young Kim ◽  
...  

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1445
Author(s):  
Taisa Nogueira Pansani ◽  
Thanh Huyen Phan ◽  
Qingyu Lei ◽  
Alexey Kondyurin ◽  
Bill Kalionis ◽  
...  

Extracellular vesicles (EVs) are nanoparticles released by cells that contain a multitude of biomolecules, which act synergistically to signal multiple cell types. EVs are ideal candidates for promoting tissue growth and regeneration. The tissue regenerative potential of EVs raises the tantalizing possibility that immobilizing EVs on implant surfaces could potentially generate highly bioactive and cell-instructive surfaces that would enhance implant integration into the body. Such surfaces could address a critical limitation of current implants, which do not promote bone tissue formation or bond bone. Here, we developed bioactive titanium surface coatings (SurfEV) using two types of EVs: secreted by decidual mesenchymal stem cells (DEVs) and isolated from fermented papaya fluid (PEVs). For each EV type, we determined the size, morphology, and molecular composition. High concentrations of DEVs enhanced cell proliferation, wound closure, and migration distance of osteoblasts. In contrast, the cell proliferation and wound closure decreased with increasing concentration of PEVs. DEVs enhanced Ca/P deposition on the titanium surface, which suggests improvement in bone bonding ability of the implant (i.e., osteointegration). EVs also increased production of Ca and P by osteoblasts and promoted the deposition of mineral phase, which suggests EVs play key roles in cell mineralization. We also found that DEVs stimulated the secretion of secondary EVs observed by the presence of protruding structures on the cell membrane. We concluded that, by functionalizing implant surfaces with specialized EVs, we will be able to enhance implant osteointegration by improving hydroxyapatite formation directly at the surface and potentially circumvent aseptic loosening of implants.


Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.


Genetics ◽  
1993 ◽  
Vol 133 (3) ◽  
pp. 711-727
Author(s):  
B K Epperson

Abstract The geographic distribution of genetic variation is an important theoretical and experimental component of population genetics. Previous characterizations of genetic structure of populations have used measures of spatial variance and spatial correlations. Yet a full understanding of the causes and consequences of spatial structure requires complete characterization of the underlying space-time system. This paper examines important interactions between processes and spatial structure in systems of subpopulations with migration and drift, by analyzing correlations of gene frequencies over space and time. We develop methods for studying important features of the complete set of space-time correlations of gene frequencies for the first time in population genetics. These methods also provide a new alternative for studying the purely spatial correlations and the variance, for models with general spatial dimensionalities and migration patterns. These results are obtained by employing theorems, previously unused in population genetics, for space-time autoregressive (STAR) stochastic spatial time series. We include results on systems with subpopulation interactions that have time delay lags (temporal orders) greater than one. We use the space-time correlation structure to develop novel estimators for migration rates that are based on space-time data (samples collected over space and time) rather than on purely spatial data, for real systems. We examine the space-time and spatial correlations for some specific stepping stone migration models. One focus is on the effects of anisotropic migration rates. Partial space-time correlation coefficients can be used for identifying migration patterns. Using STAR models, the spatial, space-time, and partial space-time correlations together provide a framework with an unprecedented level of detail for characterizing, predicting and contrasting space-time theoretical distributions of gene frequencies, and for identifying features such as the pattern of migration and estimating migration rates in experimental studies of genetic variation over space and time.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ann J. Ligocki ◽  
Wen Fury ◽  
Christian Gutierrez ◽  
Christina Adler ◽  
Tao Yang ◽  
...  

AbstractBulk RNA sequencing of a tissue captures the gene expression profile from all cell types combined. Single-cell RNA sequencing identifies discrete cell-signatures based on transcriptomic identities. Six adult human corneas were processed for single-cell RNAseq and 16 cell clusters were bioinformatically identified. Based on their transcriptomic signatures and RNAscope results using representative cluster marker genes on human cornea cross-sections, these clusters were confirmed to be stromal keratocytes, endothelium, several subtypes of corneal epithelium, conjunctival epithelium, and supportive cells in the limbal stem cell niche. The complexity of the epithelial cell layer was captured by eight distinct corneal clusters and three conjunctival clusters. These were further characterized by enriched biological pathways and molecular characteristics which revealed novel groupings related to development, function, and location within the epithelial layer. Moreover, epithelial subtypes were found to reflect their initial generation in the limbal region, differentiation, and migration through to mature epithelial cells. The single-cell map of the human cornea deepens the knowledge of the cellular subsets of the cornea on a whole genome transcriptional level. This information can be applied to better understand normal corneal biology, serve as a reference to understand corneal disease pathology, and provide potential insights into therapeutic approaches.


2014 ◽  
Vol 143 (6) ◽  
pp. 1555-1561 ◽  
Author(s):  
Van Wishingrad ◽  
Meghan K. Carr ◽  
Michael S. Pollock ◽  
Maud C. O. Ferrari ◽  
Douglas P. Chivers

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