| 1. |
- Callaway, EM, et al.
(författare)
-
A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
-
Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
|
|
| 2. |
- Loyfer, N, et al.
(författare)
-
A DNA methylation atlas of normal human cell types
- 2023
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:79447943, s. 355-
-
Tidskriftsartikel (refereegranskat)abstract
- DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells2–5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.
|
|
| 3. |
- DeMeo, Francesca E., et al.
(författare)
-
Isolating the mechanisms for asteroid surface refreshing
- 2023
-
Ingår i: Icarus. - : Elsevier. - 0019-1035 .- 1090-2643. ; 389
-
Tidskriftsartikel (refereegranskat)abstract
- Evidence is seen for young, fresh surfaces among Near-Earth and Main-Belt asteroids even though space-weathering timescales are shorter than the age of the surfaces. A number of mechanisms have been proposed to refresh asteroid surfaces on short timescales, such as planetary encounters, YORP spinup, thermal degradation, and collisions. Additionally, other factors such as grain size effects have been proposed to explain the existence of these “fresh-looking” spectra. To investigate the role each of these mechanisms may play, we collected a sample of visible and near-infrared spectra of 477 near-Earth and Mars Crosser asteroids with similar sizes and compositions — all with absolute magnitude H > 16 and within the S-complex and having olivine to pyroxene (ol/(ol+opx)) ratios >0.65. We taxonomically classify these objects in the Q (fresh) and S (weathered) classes. We find four trends in the Q/S ratio: (1) previous work demonstrated the Q/S ratio increases at smaller sizes down to H ≲16, but we find a sharp increase near H∼19 after which the ratio decreases monotonically. (2) in agreement with many previous studies, the Q/S ratio increases with decreasing perihelion distance, and we find it is non-zero for larger perihelia >1.2AU, (3) as a new finding our work reveals the Q/S ratio has a sharp, significant peak near ∼5° orbital inclination, and (4) we confirm previous findings that the Q/S ratio is higher for objects that have the possibility of encounter with Earth and Venus versus those that do not, however this finding cannot be distinguished from the perihelion trend. No single resurfacing mechanism can explain all of these trends, so multiple mechanisms are required. YORP spin-up scales with size, thermal degradation is dependent on perihelion, planetary encounters trend with inclination, perihelion and MOID, noting that asteroid–asteroid collisions are also dependent on inclination. It is likely that a combination of all four resurfacing mechanisms are needed to account for all observational trends.
|
|
| 4. |
|
|
| 5. |
- Marsset, Michaël, et al.
(författare)
-
The Debiased Compositional Distribution of MITHNEOS: Global Match between the Near-Earth and Main-belt Asteroid Populations, and Excess of D-type Near-Earth Objects
- 2022
-
Ingår i: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 163:4
-
Tidskriftsartikel (refereegranskat)abstract
- We report 491 new near-infrared spectroscopic measurements of 420 near-Earth objects (NEOs) collected on the NASA InfraRed Telescope Facility as part of the MIT-Hawaii NEO Spectroscopic Survey. These measurements were combined with previously published data from Binzel et al. and bias-corrected to derive the intrinsic compositional distribution of the overall NEO population, as well as of subpopulations coming from various escape routes (ERs) in the asteroid belt and beyond. The resulting distributions reflect well the overall compositional gradient of the asteroid belt, with decreasing fractions of silicate-rich (S- and Q-type) bodies and increasing fractions of carbonaceous (B-, C-, D- and P-type) bodies as a function of increasing ER distance from the Sun. The close compositional match between NEOs and their predicted source populations validates dynamical models used to identify ERs and argues against any strong composition change with size in the asteroid belt between ∼5 km and ∼100 m. A notable exception comes from the overabundance of D-type NEOs from the 5:2J and, to a lesser extend, the 3:1J and ν6 ERs, hinting at the presence of a large population of small D-type asteroids in the main belt. Alternatively, this excess may indicate preferential spectral evolution from D-type surfaces to C and P types as a consequence of space weathering, or point to the fact that D-type objects fragment more often than other spectral types in the NEO space. No further evidence for the existence of collisional families in the main belt, below the detection limit of current main-belt surveys, was found in this work.
|
|
