scholarly journals A probabilistic framework for cellular lineage reconstruction using single-cell 5-hydroxymethylcytosine sequencing

2019 ◽  
Author(s):  
Chatarin Wangsanuwat ◽  
Javier F. Aldeguer ◽  
Nicolas C. Rivron ◽  
Siddharth S. Dey

AbstractLineage reconstruction is central to understanding tissue development and maintenance. While powerful tools to infer cellular relationships have been developed, these methods typically have a clonal resolution that prevent the reconstruction of lineage trees at an individual cell division resolution. Moreover, these methods require a transgene, which poses a significant barrier in the study of human tissues. To overcome these limitations, we report scPECLR, a probabilistic algorithm to endogenously infer lineage trees at a single cell-division resolution using 5-hydroxymethylcytosine. When applied to 8-cell preimplantation mouse embryos, scPECLR predicts the full lineage tree with greater than 95% accuracy. Further, scPECLR can accurately extract lineage information for a majority of cells when reconstructing larger trees. Finally, we show that scPECLR can also be used to map chromosome strand segregation patterns during cell division, thereby providing a strategy to test the “immortal strand” hypothesis in stem cell biology. Thus, scPECLR provides a generalized method to endogenously reconstruct lineage trees at an individual cell-division resolution.

Development ◽  
1987 ◽  
Vol 101 (2) ◽  
pp. 403-408
Author(s):  
E.T. Mystkowska ◽  
W. Sawicki

2-cell mouse embryos were treated in vitro with a 2 h pulse of phorbol myristate acetate (PMA) at 32nd, 38th and 50th h after hCG, then chased in culture for up to 46 h. Embryos were fixed at various time intervals of chasing, then stained and inspected. Some embryos were carefully inspected with a video recording system, every 1.44s and the cell divisions (cytokinesis) as well as formation of large, single blastomeres, each from two smaller ones, were recorded. PMA pulse let to the suppression of cell divisions. The rate of the suppression was time dependent: with a delay of 0–1, 12 and 18 h between the PMA pulse and time of scheduled cell division about 99, 87 and 44% of 2-cell embryos remained at this stage of development, for at least 10 h, respectively, and 90, 58 and 12% of their blastomeres revealed binuclearity. Since we found that PMA-mediated formation of binuclearity was not the effect of cell fusions, it was assumed that the inhibition of cytokinesis preceded by karyokinesis was responsible for binuclearity. PMA effect on cell divisions was reversible. PMA-treated embryos revealed formation of large, single blastomeres, each from two smaller ones. If cell division appeared after PMA pulse, in about 52% of 3- to 6-cell embryos, the large blastomere formation was recorded in the course of the subsequent 38 h. Large blastomere formation was concluded to be the result of either cell fusion or reversion of incompleted cytokinesis brought about by PMA.


1989 ◽  
Vol 51 (3) ◽  
pp. 513-517 ◽  
Author(s):  
Leeanda J. Wilton ◽  
Jillian M. Shaw ◽  
Alan O. Trounson

2020 ◽  
Author(s):  
Ivan Croydon Veleslavov ◽  
Michael P.H. Stumpf

AbstractSingle cell transcriptomics has laid bare the heterogeneity of apparently identical cells at the level of gene expression. For many cell-types we now know that there is variability in the abundance of many transcripts, and that average transcript abun-dance or average gene expression can be a unhelpful concept. A range of clustering and other classification methods have been proposed which use the signal in single cell data to classify, that is assign cell types, to cells based on their transcriptomic states. In many cases, however, we would like to have not just a classifier, but also a set of interpretable rules by which this classification occurs. Here we develop and demonstrate the interpretive power of one such approach, which sets out to establish a biologically interpretable classification scheme. In particular we are interested in capturing the chain of regulatory events that drive cell-fate decision making across a lineage tree or lineage sequence. We find that suitably defined decision trees can help to resolve gene regulatory programs involved in shaping lineage trees. Our approach combines predictive power with interpretabilty and can extract logical rules from single cell data.


2018 ◽  
Author(s):  
Nikolaos Papadopoulos ◽  
R. Gonzalo Parra ◽  
Johannes Söding

BackgroundSingle-cell RNA sequencing (scRNA-seq) is an enabling technology for the study of cellular differentiation and heterogeneity. From snapshots of the transcriptomic profiles of differentiating single cells, the cellular lineage tree that leads from a progenitor population to multiple types of differentiated cells can be derived. The underlying lineage trees of most published datasets are linear or have a single branchpoint, but many studies with more complex lineage trees will soon become available. To test and further develop tools for lineage tree reconstruction, we need test datasets with known trees.ResultsPROSSTT can simulate scRNA-seq datasets for differentiation processes with lineage trees of any desired complexity, noise level, noise model, and size. PROSSTT also provides scripts to quantify the quality of predicted lineage trees.Availabilityhttps://github.com/soedinglab/[email protected]


2019 ◽  
Author(s):  
Attila Csordas

The argument makes the case for cell lineage trees and cell tree dynamics to be considered as the central structure and process of understanding organismal level, multicellular biological aging. The limiting challenge of counteracting biological aging is comprehensive organismal rejuvenation. The central theoretical problem of comprehensive biological rejuvenation is to find an algorithm to restore the balance and maintain the healthy dynamics of the aging organismal cell lineage tree. The most comprehensive medical solution of biological aging needs to use individual cell lineage trees as a central tool for diagnosis and treatment.


2019 ◽  
Author(s):  
Attila Csordas

The argument makes the case for cell lineage trees and cell tree dynamics to be considered as the central structure and process of understanding organismal level, multicellular biological aging. The limiting challenge of counteracting biological aging is comprehensive organismal rejuvenation. The central theoretical problem of comprehensive biological rejuvenation is to find an algorithm to restore the balance and maintain the healthy dynamics of the aging organismal cell lineage tree. The most comprehensive medical solution of biological aging needs to use individual cell lineage trees as a central tool for diagnosis and treatment.


2019 ◽  
Author(s):  
Attila Csordas

The argument makes the case for cell lineage trees and cell tree dynamics to be considered as the central structure and process of understanding organismal level, multicellular biological aging. The limiting challenge of counteracting biological aging is comprehensive organismal rejuvenation. The central theoretical problem of comprehensive biological rejuvenation is to find an algorithm to restore the balance and maintain the healthy dynamics of the aging organismal cell lineage tree. The most comprehensive medical solution of biological aging needs to use individual cell lineage trees as a central tool for diagnosis and treatment.


1998 ◽  
Vol 198 (1) ◽  
pp. 105-115 ◽  
Author(s):  
Ning Chai ◽  
Yogesh Patel ◽  
Kristine Jacobson ◽  
Jill McMahon ◽  
Andrew McMahon ◽  
...  

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