lineage trees
Recently Published Documents


TOTAL DOCUMENTS

91
(FIVE YEARS 41)

H-INDEX

15
(FIVE YEARS 4)

Author(s):  
Naoki Konno ◽  
Yusuke Kijima ◽  
Keito Watano ◽  
Soh Ishiguro ◽  
Keiichiro Ono ◽  
...  

2021 ◽  
Author(s):  
Allen W. Lynch ◽  
Christina V. Theodoris ◽  
Henry Long ◽  
Myles Brown ◽  
X. Shirley Liu ◽  
...  

Rigorously comparing gene expression and chromatin accessibility in the same single cells could illuminate the logic of how coupling or decoupling of these mechanisms regulates fate commitment. Here, we present MIRA: Probabilistic Multimodal Models for Integrated Regulatory Analysis, a comprehensive methodology that systematically contrasts transcription and accessibility to infer the regulatory circuitry driving cells along developmental trajectories. MIRA leverages joint topic modeling of cell states and regulatory potential modeling of individual gene loci. MIRA thereby represents cell states in an efficient and interpretable latent space, infers high fidelity lineage trees, determines key regulators of fate decisions at branch points, and exposes the variable influence of local accessibility on transcription at distinct loci. Applied to epidermal maintenance differentiation and embryonic brain development from two different multimodal platforms, MIRA revealed that early developmental genes were tightly regulated by local chromatin landscape whereas terminal fate genes were titrated without requiring extensive chromatin remodeling.


2021 ◽  
Author(s):  
Elena Schaberg ◽  
Magdalena Götz ◽  
Andreas Faissner

Abstract Adult neurogenesis has been described in two canonical regions of the adult central nervous system (CNS) of rodents, the subgranular zone (SGZ) of the hippocampus and the subependymal zone (SEZ) of the lateral ventricles. The stem cell niche of the SEZ provides a privileged environment composed of a specialized extracellular matrix (ECM) that comprises the glycoproteins tenascin-C (Tnc) and laminin-1 (LN1). In the present study, we investigated the function of these ECM glycoproteins in the adult stem cell niche. Adult neural stem cells (aNSPCs) of the SEZ were prepared from wildtype (Tnc+/+) and Tnc knockout (Tnc-/-) mice and analyzed using molecular and cell biological approaches. A delayed maturation of aNSPCs in Tnc-/- tissue was reflected by a reduced capacity to form neurospheres in response to epidermal growth factor (EGF). In order to examine a potential influence of the ECM on cell proliferation, aNSPCs of both genotypes were studied by cell tracking using digital video microscopy. aNSPCs were cultivated on three different substrates, namely poly-D-Lysine (PDL) and PDL replenished with either LN1 or Tnc for up to six days in vitro. On each of the three substrates aNSPCs displayed lineage trees that could be investigated with regard to cell cycle length. The latter appeared reduced in Tnc-/- aNSPCs on PDL and LN1 substrates, less so on Tnc that seemed to compensate the absence of the ECM compound to some extent. Close inspection of the lineage trees revealed a subpopulation of late dividing aNSPCslate that engaged into cycling after a notable delay. aNSPCslate exhibited a clearly different morphology, with a larger cell body and conspicuous processes. aNSPCslate reiterated the reduction in cell cycle length on all substrates tested, which was not rescued on Tnc substrates. When the migratory activity of aNSPC-derived progeny was determined, Tnc-/- neuroblasts displayed significantly longer migration tracks. This was traced to an increased rate of migration episodes compared to the wildtype cells that rested for longer time periods. We conclude that Tnc intervenes in the proliferation of aNSPCs and modulates the motility of neuroblasts in the niche of the SEZ.


Author(s):  
Max A. Betjes ◽  
Xuan Zheng ◽  
Rutger N. U. Kok ◽  
Jeroen S. van Zon ◽  
Sander J. Tans

Organoids have emerged as powerful model systems to study organ development and regeneration at the cellular level. Recently developed microscopy techniques that track individual cells through space and time hold great promise to elucidate the organizational principles of organs and organoids. Applied extensively in the past decade to embryo development and 2D cell cultures, cell tracking can reveal the cellular lineage trees, proliferation rates, and their spatial distributions, while fluorescent markers indicate differentiation events and other cellular processes. Here, we review a number of recent studies that exemplify the power of this approach, and illustrate its potential to organoid research. We will discuss promising future routes, and the key technical challenges that need to be overcome to apply cell tracking techniques to organoid biology.


2021 ◽  
Author(s):  
Gustavo de Medeiros ◽  
Raphael Ortiz ◽  
Petr Strnad ◽  
Andrea Boni ◽  
Francisca Maurer ◽  
...  

We present an imaging framework capable of turning long term light-sheet imaging of organoids into digital organoids. The framework takes advantage of deep learning techniques to faithfully segment single organoids, their lumen, cells and nuclei in 3D and over long periods of time. In parallel, large lineage trees for each organoid are predicted and corrected to iteratively improve the tracking and segmentation performances over time. To visualize the extracted information, we developed a web-based 'Digital Organoid Viewer' that allows a unique understanding of the multivariate and multiscale data by linking 2D lineage trees with the corresponding 3D segmentation meshes. We also backtracked single cells of interest after fixation obtaining detailed information about their history within the entire organoid context. Furthermore, we show nuclei merging events that arise from cytokinesis failure and that these polyploid never reside in the intestinal crypt, hinting at a tissue scale control and feedback on cellular fidelity. Molecularly, these cytokinesis failures depend on a regenerative state of the organoids and are regulated by Lats1 and RXR and we propose a model of tissue integrity by multi-scale check points. This discovery sheds light on the robustness of a regenerative YAP cellular state, questioning the role of polyploidy in intestinal regeneration.


Science ◽  
2021 ◽  
Vol 372 (6538) ◽  
pp. eabb3099
Author(s):  
Ke-Huan K. Chow ◽  
Mark W. Budde ◽  
Alejandro A. Granados ◽  
Maria Cabrera ◽  
Shinae Yoon ◽  
...  

During multicellular development, spatial position and lineage history play powerful roles in controlling cell fate decisions. Using a serine integrase–based recording system, we engineered cells to record lineage information in a format that can be read out in situ. The system, termed integrase-editable memory by engineered mutagenesis with optical in situ readout (intMEMOIR), allowed in situ reconstruction of lineage relationships in cultured mouse cells and flies. intMEMOIR uses an array of independent three-state genetic memory elements that can recombine stochastically and irreversibly, allowing up to 59,049 distinct digital states. It reconstructed lineage trees in stem cells and enabled simultaneous analysis of single-cell clonal history, spatial position, and gene expression in Drosophila brain sections. These results establish a foundation for microscopy-readable lineage recording and analysis in diverse systems.


Science ◽  
2021 ◽  
Vol 371 (6535) ◽  
pp. 1245-1248
Author(s):  
Liana Fasching ◽  
Yeongjun Jang ◽  
Simone Tomasi ◽  
Jeremy Schreiner ◽  
Livia Tomasini ◽  
...  

Mosaic mutations can be used to track cell lineages in humans. We used cell cloning to analyze embryonic cell lineages in two living individuals and a postmortem human specimen. Of 10 reconstructed postzygotic divisions, none resulted in balanced contributions of daughter lineages to tissues. In both living individuals, one of two lineages from the first cleavage was dominant across tissues, with 90% frequency in blood. We propose that the efficiency of DNA repair contributes to lineage imbalance. Allocation of lineages in postmortem brain correlated with anterior-posterior axis, associating lineage history with cell fate choices in embryos. We establish a minimally invasive framework for defining cell lineages in any living individual, which paves the way for studying their relevance in health and disease.


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Jean Feng ◽  
William S. DeWitt III ◽  
Aaron McKenna ◽  
Noah Simon ◽  
Amy D. Willis ◽  
...  

2021 ◽  
Vol 54 (7) ◽  
pp. 150-155
Author(s):  
Aline Marguet ◽  
Eugenio Cinquemani

Sign in / Sign up

Export Citation Format

Share Document