A mathematical insight into cell labelling experiments for clonal analysis

Picco, Noemi; Hippenmeyer, Simon; Rodarte, Julio J.; Streicher, Carmen; Molnár, Zoltán; Maini, Philip K.; Woolley, Thomas E.

doi:10.1111/joa.13001

Cited by 8 publications

(10 citation statements)

References 37 publications

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“…Recent lineage analysis experiments and mathematical modeling inquiries helped to increase our understanding how these processes are regulated (Beattie & Hippenmeyer, ; Picco et al. ).…”

Section: Specification Of Pyramidal Neurons: Layers Function Arealimentioning

confidence: 99%

New insights into the development of the human cerebral cortex

et al. 2019

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The cerebral cortex constitutes more than half the volume of the human brain and is presumed to be responsible for the neuronal computations underlying complex phenomena, such as perception, thought, language, attention, episodic memory and voluntary movement. Rodent models are extremely valuable for the investigation of brain development, but cannot provide insight into aspects that are unique or highly derived in humans. Many human psychiatric and neurological conditions have developmental origins but cannot be studied adequately in animal models. The human cerebral cortex has some unique genetic, molecular, cellular and anatomical features, which need to be further explored. The Anatomical Society devoted its summer meeting to the topic of Human Brain Development in June 2018 to tackle these important issues. The meeting was organized by Gavin Clowry (Newcastle University) and Zoltán Molnár (University of Oxford), and held at St John's College, Oxford. The participants provided a broad overview of the structure of the human brain in the context of scaling relationships across the brains of mammals, conserved principles and recent changes in the human lineage. Speakers considered how neuronal progenitors diversified in human to generate an increasing variety of cortical neurons. The formation of the earliest cortical circuits of the earliest generated neurons in the subplate was discussed together with their involvement in neurodevelopmental pathologies. Gene expression networks and susceptibility genes associated to neurodevelopmental diseases were discussed and compared with the networks that can be identified in organoids developed from induced pluripotent stem cells that recapitulate some aspects of in vivo development. New views were discussed on the specification of glutamatergic pyramidal and γ‐aminobutyric acid (GABA)ergic interneurons. With the advancement of various in vivo imaging methods, the histopathological observations can be now linked to in vivo normal conditions and to various diseases. Our review gives a general evaluation of the exciting new developments in these areas. The human cortex has a much enlarged association cortex with greater interconnectivity of cortical areas with each other and with an expanded thalamus. The human cortex has relative enlargement of the upper layers, enhanced diversity and function of inhibitory interneurons and a highly expanded transient subplate layer during development. Here we highlight recent studies that address how these differences emerge during development focusing on diverse facets of our evolution.

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“…Recent lineage analysis experiments and mathematical modeling inquiries helped to increase our understanding how these processes are regulated (Beattie & Hippenmeyer, ; Picco et al. ).…”

Section: Specification Of Pyramidal Neurons: Layers Function Arealimentioning

confidence: 99%

New insights into the development of the human cerebral cortex

et al. 2019

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“…It would be interesting to compare estimates of transition rates with in vivo case, where, in certain contexts, lineage tracing data can be used to identify clones. A potential application of our model comparison approach in this context would be to compare the number of stages in stem/progenitor cell lineages to best explain observed clone size distributions [34].…”

Section: Future Workmentioning

confidence: 99%

Coupled differentiation and division of embryonic stem cells inferred from clonal snapshots

Kursawe

Tsakiridis

et al. 2020

Phys. Biol.

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The deluge of single-cell data obtained by sequencing, imaging and epigenetic markers has led to an increasingly detailed description of cell state. However, it remains challenging to identify how cells transition between different states, in part because data are typically limited to snapshots in time. A prerequisite for inferring cell state transitions from such snapshots is to distinguish whether transitions are coupled to cell divisions. To address this, we present two minimal branching process models of cell division and differentiation in a well-mixed population. These models describe dynamics where differentiation and division are coupled or uncoupled. For each model, we derive analytic expressions for each subpopulation’s mean and variance and for the likelihood, allowing exact Bayesian parameter inference and model selection in the idealised case of fully observed trajectories of differentiation and division events. In the case of snapshots, we present a sample path algorithm and use this to predict optimal temporal spacing of measurements for experimental design. We then apply this methodology to an in vitro dataset assaying the clonal growth of epiblast stem cells in culture conditions promoting self-renewal or differentiation. Here, the larger number of cell states necessitates approximate Bayesian computation. For both culture conditions, our inference supports the model where cell state transitions are coupled to division. For culture conditions promoting differentiation, our analysis indicates a possible shift in dynamics, with these processes becoming more coupled over time.

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“…The temporally controlled induction of MADM with its dual marker property provides exact and unique information not only about birth dates of clones but also regarding their cell division patterns. Thus, MADM has been frequently utilized in the past to study the proliferation behavior of progenitor stem cells in a variety of tissues -including embryonic and adult neural stem cells (Beattie et al 2017;Bonaguidi et al 2011;Espinosa and Luo 2008;Gao et al 2014;Kaplan et al 2017;Liang et al 2013;Llorca et al 2019;Lv et al 2019;Mayer et al 2015;Mihalas and Hevner 2018;Ortiz-Alvarez et al 2019;Picco et al 2019;Shi et al 2017;Wong et al 2018); cardiomyocyte- (Ali et al 2014;Devine et al 2014;Mohamed et al 2018) and pancreatic progenitor cells (Brennand et al 2007;Desgraz and Herrera 2009;Salpeter et al 2010); progenitors in the developing kidney (Riccio et al 2016); and mesenchymal progenitors in the developing lung (Kumar et al 2014). MADM enables high resolution single cell/clonal labeling and permits tracing of complex morphogenetic processes in 4D by using live-imaging over prolonged periods besides analysis of static time points (Hippenmeyer et al 2010;Riccio et al 2016).…”

Section: Introductionmentioning

confidence: 99%

A Genome-wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis

Contreras

Davaatseren

Amberg

et al. 2020

Preprint

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Mosaic Analysis with Double Markers (MADM) offers a unique approach to visualize and concomitantly manipulate genetically-defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage; single-cell morphology and physiology; genomic imprinting phenotypes; and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM could only be applied to <25% of all mouse genes on select chromosomes thus far. To overcome this limitation, we generated transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validated their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond proof-of-principle, we applied our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We found striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division.

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A mathematical insight into cell labelling experiments for clonal analysis

Cited by 8 publications

References 37 publications

New insights into the development of the human cerebral cortex

New insights into the development of the human cerebral cortex

Coupled differentiation and division of embryonic stem cells inferred from clonal snapshots

A Genome-wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis

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