| 1. |
- Lohoff, T., et al.
(författare)
-
Integration of spatial and single-cell transcriptomic data elucidates mouse organogenesis
- 2022
-
Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 40, s. 74-85
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular profiling of single cells has advanced our knowledge of the molecular basis of development. However, current approaches mostly rely on dissociating cells from tissues, thereby losing the crucial spatial context of regulatory processes. Here, we apply an image-based single-cell transcriptomics method, sequential fluorescence in situ hybridization (seqFISH), to detect mRNAs for 387 target genes in tissue sections of mouse embryos at the 8–12 somite stage. By integrating spatial context and multiplexed transcriptional measurements with two single-cell transcriptome atlases, we characterize cell types across the embryo and demonstrate that spatially resolved expression of genes not profiled by seqFISH can be imputed. We use this high-resolution spatial map to characterize fundamental steps in the patterning of the midbrain–hindbrain boundary (MHB) and the developing gut tube. We uncover axes of cell differentiation that are not apparent from single-cell RNA-sequencing (scRNA-seq) data, such as early dorsal–ventral separation of esophageal and tracheal progenitor populations in the gut tube. Our method provides an approach for studying cell fate decisions in complex tissues and development. © 2021, The Author(s).
|
|
| 2. |
- Giesers, B., et al.
(författare)
-
A stellar census in globular clusters with MUSE: Binaries in NGC 3201
- 2019
-
Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 632
-
Tidskriftsartikel (refereegranskat)abstract
- We utilise multi-epoch MUSE spectroscopy to study binary stars in the core of the Galactic globular cluster NGC 3201. Our sample consists of 3553 stars with 54 883 spectra in total comprising 3200 main-sequence stars up to 4 magnitudes below the turn-off. Each star in our sample has between 3 and 63 (with a median of 14) reliable radial velocity measurements within five years of observations. We introduce a statistical method to determine the probability of a star showing radial velocity variations based on the whole inhomogeneous radial velocity sample. Using HST photometry and an advanced dynamical MOCCA simulation of this specific cluster we overcome observational biases that previous spectroscopic studies had to deal with. This allows us to infer a binary frequency in the MUSE field of view and enables us to deduce the underlying true binary frequency of (6.75 ± 0.72)% in NGC 3201. The comparison of the MUSE observations with the MOCCA simulation suggests a large portion of primordial binaries. We can also confirm a radial increase in the binary fraction towards the cluster centre due to mass segregation. We discovered that in the core of NGC 3201 at least (57.5 ± 7.9)% of blue straggler stars are in a binary system. For the first time in a study of globular clusters, we were able to fit Keplerian orbits to a significant sample of 95 binaries. We present the binary system properties of eleven blue straggler stars and the connection to SX Phoenicis-type stars. We show evidence that two blue straggler formation scenarios, the mass transfer in binary (or triple) star systems and the coalescence due to binary-binary interactions, are present in our data. We also describe the binary and spectroscopic properties of four sub-subgiant (or red straggler) stars. Furthermore, we discovered two new black hole candidates with minimum masses (M sin i) of (7.68 ± 0.50) M⊙, (4.4 ± 2.8) M⊙, and refine the minimum mass estimate on the already published black hole to (4.53 ± 0.21) M⊙. These black holes are consistent with an extensive black hole subsystem hosted by NGC 3201.
|
|
| 3. |
|
|
| 4. |
- Takahashi, M., et al.
(författare)
-
Reconciling Flux Experiments for Quantitative Modeling of Normal and Malignant Hematopoietic Stem/Progenitor Dynamics
- 2021
-
Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 16:4, s. 741-753
-
Tidskriftsartikel (refereegranskat)abstract
- Hematopoiesis serves as a paradigm for how homeostasis is maintained within hierarchically organized cell populations. However, important questions remain as to the contribution of hematopoietic stem cells (HSCs) toward maintaining steady state hematopoiesis. A number of in vivo lineage labeling and propagation studies have given rise to contradictory interpretations, leaving key properties of stem cell function unresolved. Using processed flow cytometry data coupled with a biology-driven modeling approach, we show that in vivo flux experiments that come from different laboratories can all be reconciled into a single unifying model, even though they had previously been interpreted as being contradictory. We infer from comparative analysis that different transgenic models display distinct labeling efficiencies across a heterogeneous HSC pool, which we validate by marker gene expression associated with HSC function. Finally, we show how the unified model of HSC differentiation can be used to simulate clonal expansion in the early stages of leukemogenesis. © 2021 The Authors
|
|
| 5. |
- Ton, M. L. N., et al.
(författare)
-
Single cell genomics and developmental biology: moving beyond the generation of cell type catalogues
- 2020
-
Ingår i: Current Opinion in Genetics and Development. - : Elsevier BV. - 0959-437X. ; 64, s. 66-71
-
Tidskriftsartikel (refereegranskat)abstract
- Major developmental processes such as gastrulation and early embryogenesis rely on a complex network of cell–cell interactions, chromatin remodeling, and transcriptional regulators. This makes it challenging to study early development when using bulk populations of cells. Recent advances in single-cell technologies have allowed researchers to better understand the interactions between different molecular modalities and the heterogeneities within classically defined cell types. As new single-cell technologies mature, they have the potential of providing a step-change in our understanding of embryogenesis. In this review, we summarize recent advances in single-cell technologies with particular focus on those that lend insight into early organogenesis. We then discuss current pitfalls and implications for future research. © 2020 Elsevier Ltd
|
|
