Revealing routes of cellular differentiation by single-cell RNA-seq

Differentiation of multipotent stem cells is controlled by the intricate regulatory interactions of thousands of genes. It remains one of the major challenges to understand how nature has designed such robust and reproducible regulatory mechanisms. Knowing the detailed structure of the underlying lineage trees is the basis for investigating the molecular control of this process. The recent availability of large-scale sensitive single-cell RNAseq protocols has enabled the generation of snapshot data covering the entire spectrum of cell states in a systemof interest. Consequently, a large number of computational methods for the reconstruction of cellular differentiation trajectories have been developed. Here, I will provide a detailed overview of the concepts and ideas behind some of these algorithms and discuss the particular aspects addressed by each method

Galileo dust data from the jovian system: 2000 to 2003

The Galileo spacecraft was orbiting Jupiter between Dec 1995 and Sep 2003. The Galileo dust detector monitored the jovian dust environment between about 2 and 370 R_J (jovian radius R_J = 71492 km). We present data from the Galileo dust instrument for the period January 2000 to September 2003. We report on the data of 5389 particles measured between 2000 and the end of the mission in 2003. The majority of the 21250 particles for which the full set of measured impact parameters (impact time, impact direction, charge rise times, charge amplitudes, etc.) was transmitted to Earth were tiny grains (about 10 nm in radius), most of them originating from Jupiter's innermost Galilean moon Io. Their impact rates frequently exceeded 10 min^-1. Surprisingly large impact rates up to 100 min^-1 occurred in Aug/Sep 2000 when Galileo was at about 280 R_J from Jupiter. This peak in dust emission appears to coincide with strong changes in the release of neutral gas from the Io torus. Strong variability in the Io dust flux was measured on timescales of days to weeks, indicating large variations in the dust release from Io or the Io torus or both on such short timescales. Galileo has detected a large number of bigger micron-sized particles mostly in the region between the Galilean moons. A surprisingly large number of such bigger grains was measured in March 2003 within a 4-day interval when Galileo was outside Jupiter's magnetosphere at approximately 350 R_J jovicentric distance. Two passages of Jupiter's gossamer rings in 2002 and 2003 provided the first actual comparison of in-situ dust data from a planetary ring with the results inferred from inverting optical images.Comment: 59 pages, 13 figures, 6 tables, submitted to Planetary and Space Scienc

In Situ Measurements of Interstellar Dust

We present the mass distribution of interstellar grains measured in situ by the Galileo and Ulysses spaceprobes as cumulative flux. The derived in situ mass distribution per logarithmic size interval is compared to the distribution determined by fitting extinction measurements. Large grains measured in situ contribute significantly to the overall mass of dust in the local interstellar cloud. The problem of a dust-to-gas mass ratio that contradicts cosmic abundances is discussed.Comment: 4 pages and two figure

EBF1-deficient bone marrow stroma elicits persistent changes in HSC potential

Crosstalk between mesenchymal stromal cells (MSCs) and hematopoietic stem cells (HSCs) is essential for hematopoietic homeostasis and lineage output. Here, we investigate how transcriptional changes in bone marrow (BM) MSCs result in long-lasting effects on HSCs. Single-cell analysis of Cxcl12-abundant reticular (CAR) cells and PDGFRα+Sca1+ (PαS) cells revealed an extensive cellular heterogeneity but uniform expression of the transcription factor gene Ebf1. Conditional deletion of Ebf1 in these MSCs altered their cellular composition, chromatin structure and gene expression profiles, including the reduced expression of adhesion-related genes. Functionally, the stromal-specific Ebf1 inactivation results in impaired adhesion of HSCs, leading to reduced quiescence and diminished myeloid output. Most notably, HSCs residing in the Ebf1-deficient niche underwent changes in their cellular composition and chromatin structure that persist in serial transplantations. Thus, genetic alterations in the BM niche lead to long-term functional changes of HSCs

One year of Galileo dust data from the Jovian system: 1996

The dust detector system onboard Galileo records dust impacts in circumjovian space since the spacecraft has been injected into a bound orbit about Jupiter in December 1995. This is the sixth in a series of papers dedicated to presenting Galileo and Ulysses dust data. We present data from the Galileo dust instrument for the period January to December 1996 when the spacecraft completed four orbits about Jupiter (G1, G2, C3 and E4). Data were obtained as high resolution realtime science data or recorded data during a time period of 100 days, or via memory read-outs during the remaining times. Because the data transmission rate of the spacecraft is very low, the complete data set (i. e. all parameters measured by the instrument during impact of a dust particle) for only 2% (5353) of all particles detected could be transmitted to Earth; the other particles were only counted. Together with the data for 2883 particles detected during Galileo's interplanetary cruise and published earlier, complete data of 8236 particles detected by the Galileo dust instrument from 1989 to 1996 are now available. The majority of particles detected are tiny grains (about 10 nm in radius) originating from Jupiter's innermost Galilean moon Io. These grains have been detected throughout the Jovian system and the highest impact rates exceeded $\rm 100 min^{-1}$. A small number of grains has been detected in the close vicinity of the Galilean moons Europa, Ganymede and Callisto which belong to impact-generated dust clouds formed by (mostly submicrometer sized) ejecta from the surfaces of the moons (Kr\"uger et al., Nature, 399, 558, 1999). Impacts of submicrometer to micrometer sized grains have been detected thoughout the Jovian system and especially in the region between the Galilean moons.Comment: accepted for Planetary and Space Science, 33 pages, 6 tables, 10 figure

Ion-acoustic solitary waves and shocks in a collisional dusty negative ion plasma

We study the effects of ion-dust collisions and ion kinematic viscosities on the linear ion-acoustic instability as well as the nonlinear propagation of small amplitude solitary waves and shocks (SWS) in a negative ion plasma with immobile charged dusts. {The existence of two linear ion modes, namely the `fast' and `slow' waves is shown, and their properties are analyzed in the collisional negative ion plasma.} {Using the standard reductive perturbation technique, we derive a modified Korteweg-de Vries-Burger (KdVB) equation which describes the evolution of small amplitude SWS.} {The profiles of the latter are numerically examined with parameters relevant for laboratory and space plasmas where charged dusts may be positively or negatively charged.} It is found that negative ion plasmas containing positively charged dusts support the propagation of SWS with negative potential. However, the perturbations with both positive and negative potentials may exist when dusts are negatively charged. The results may be useful for the excitation of SWS in laboratory negative ion plasmas as well as for observation in space plasmas where charged dusts may be positively or negatively charged.Comment: 13 pages, 9 figures; To appear in Physical Review

Estimating the contribution of assembly activity to cortical dynamics from spike and population measures

The hypothesis that cortical networks employ the coordinated activity of groups of neurons, termed assemblies, to process information is debated. Results from multiple single-unit recordings are not conclusive because of the dramatic undersampling of the system. However, the local field potential (LFP) is a mesoscopic signal reflecting synchronized network activity. This raises the question whether the LFP can be employed to overcome the problem of undersampling. In a recent study in the motor cortex of the awake behaving monkey based on the locking of coincidences to the LFP we determined a lower bound for the fraction of spike coincidences originating from assembly activation. This quantity together with the locking of single spikes leads to a lower bound for the fraction of spikes originating from any assembly activity. Here we derive a statistical method to estimate the fraction of spike synchrony caused by assemblies—not its lower bound—from the spike data alone. A joint spike and LFP surrogate data model demonstrates consistency of results and the sensitivity of the method. Combining spike and LFP signals, we obtain an estimate of the fraction of spikes resulting from assemblies in the experimental data

Four years of Ulysses dust data: 1996 to 1999

The Ulysses spacecraft is orbiting the Sun on a highly inclined ellipse ($i = 79^{\circ}$, perihelion distance 1.3 AU, aphelion distance 5.4 AU). Between January 1996 and December 1999 the spacecraft was beyond 3 AU from the Sun and crossed the ecliptic plane at aphelion in May 1998. In this four-year period 218 dust impacts were recorded with the dust detector on board. We publish and analyse the complete data set of both raw and reduced data for particles with masses $\rm 10^{-16} g$ to $\rm 10^{-8}$ g. Together with 1477 dust impacts recorded between launch of Ulysses and the end of 1995 published earlier \cite{gruen1995c,krueger1999b}, a data set of 1695 dust impacts detected with the Ulysses sensor between October 1990 and December 1999 is now available. The impact rate measured between 1996 and 1999 was relatively constant with about 0.2 impacts per day. The impact direction of the majority of the impacts is compatible with particles of interstellar origin, the rest are most likely interplanetary particles. The observed impact rate is compared with a model for the flux of interstellar dust particles. The flux of particles several micrometers in size is compared with the measurements of the dust instruments on board Pioneer 10 and Pioneer 11 beyond 3 AU (Humes 1980, JGR, 85, 5841--5852, 1980). Between 3 and 5 AU, Pioneer results predict that Ulysses should have seen five times more ($\rm \sim 10 \mu m$ sized) particles than actually detected.Comment: accepted by Planetary and Space Science, 22 pages, 8 figures (1 colour figure

Developmental dynamics of two bipotent thymic epithelial progenitor types

T cell development in the thymus is essential for cellular immunity and depends on the organotypic thymic epithelial microenvironment. In comparison with other organs, the size and cellular composition of the thymus are unusually dynamic, as exemplified by rapid growth and high T cell output during early stages of development, followed by a gradual loss of functional thymic epithelial cells and diminished naive T cell production with age. Single-cell RNA sequencing (scRNA-seq) has uncovered an unexpected heterogeneity of cell types in the thymic epithelium of young and aged adult mice; however, the identities and developmental dynamics of putative pre- and postnatal epithelial progenitors have remained unresolved. Here we combine scRNA-seq and a new CRISPR–Cas9-based cellular barcoding system in mice to determine qualitative and quantitative changes in the thymic epithelium over time. This dual approach enabled us to identify two principal progenitor populations: an early bipotent progenitor type biased towards cortical epithelium and a postnatal bipotent progenitor population biased towards medullary epithelium. We further demonstrate that continuous autocrine provision of Fgf7 leads to sustained expansion of thymic microenvironments without exhausting the epithelial progenitor pools, suggesting a strategy to modulate the extent of thymopoietic activity

Nanodust detection near 1 AU from spectral analysis of Cassini/RPWS radio data

Nanodust grains of a few nanometer in size are produced near the Sun by collisional break-up of larger grains and picked-up by the magnetized solar wind. They have so far been detected at 1 AU by only the two STEREO spacecraft. Here we analyze the spectra measured by the radio and plasma wave instrument onboard Cassini during the cruise phase close to Earth orbit; they exhibit bursty signatures similar to those observed by the same instrument in association to nanodust stream impacts on Cassini near Jupiter. The observed wave level and spectral shape reveal impacts of nanoparticles at about 300 km/s, with an average flux compatible with that observed by the radio and plasma wave instrument onboard STEREO and with the interplanetary flux models