scholarly journals Single-Cell Lineage Tracing Reveals that Oriented Cell Division Contributes to Trabecular Morphogenesis and Regional Specification

Cell Reports ◽  
2016 ◽  
Vol 15 (1) ◽  
pp. 158-170 ◽  
Author(s):  
Jingjing Li ◽  
Lianjie Miao ◽  
David Shieh ◽  
Ernest Spiotto ◽  
Jian Li ◽  
...  
Keyword(s):  
Cell Division ◽  
Single Cell ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Oriented Cell Division

scholarly journals Stem cell dynamics in mouse hair follicles: A story from cell division counting and single cell lineage tracing

Cell Cycle ◽  
2010 ◽  
Vol 9 (8) ◽  
pp. 1504-1510 ◽  
Author(s):  
Ying V. Zhang ◽  
Brian S. White ◽  
David I. Shalloway ◽  
Tudorita Tumbar
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Single Cell ◽  
Cell Lineage ◽  
Hair Follicles ◽  
Lineage Tracing ◽  
Cell Dynamics

scholarly journals Single-cell lineage tracing approaches in hematology research: technical considerations

2020 ◽  
Vol 89 ◽  
pp. 26-36 ◽  
Author(s):  
Joana Carrelha ◽  
Dawn S. Lin ◽  
Alejo E. Rodriguez-Fraticelli ◽  
Tiago C. Luis ◽  
Adam C. Wilkinson ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Technical Considerations

scholarly journals Single cell lineage tracing reveals a role for TgfβR2 in intestinal stem cell dynamics and differentiation

2016 ◽  
Vol 113 (43) ◽  
pp. 12192-12197 ◽  
Author(s):  
Jared M. Fischer ◽  
Peter P. Calabrese ◽  
Ashleigh J. Miller ◽  
Nina M. Muñoz ◽  
William M. Grady ◽  
...  
Keyword(s):  
Single Cell ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Cell Lineage ◽  
Transforming Growth Factor Β ◽  
Lineage Tracing ◽  
Secretory Cells ◽  
Cancer Tissue ◽  
Tgfβ Signaling

Intestinal stem cells (ISCs) are maintained by a niche mechanism, in which multiple ISCs undergo differential fates where a single ISC clone ultimately occupies the niche. Importantly, mutations continually accumulate within ISCs creating a potential competitive niche environment. Here we use single cell lineage tracing following stochastic transforming growth factor β receptor 2 (TgfβR2) mutation to show cell autonomous effects of TgfβR2 loss on ISC clonal dynamics and differentiation. Specifically, TgfβR2 mutation in ISCs increased clone survival while lengthening times to monoclonality, suggesting that Tgfβ signaling controls both ISC clone extinction and expansion, independent of proliferation. In addition, TgfβR2 loss in vivo reduced crypt fission, irradiation-induced crypt regeneration, and differentiation toward Paneth cells. Finally, altered Tgfβ signaling in cultured mouse and human enteroids supports further the in vivo data and reveals a critical role for Tgfβ signaling in generating precursor secretory cells. Overall, our data reveal a key role for Tgfβ signaling in regulating ISCs clonal dynamics and differentiation, with implications for cancer, tissue regeneration, and inflammation.

scholarly journals A lineage-tracing tool to map the fate of hypoxic tumour cells

2020 ◽  
Author(s):  
Jenny A.F. Vermeer ◽  
Jonathan Ient ◽  
Bostjan Markelc ◽  
Jakob Kaeppler ◽  
Lydie M.O. Barbeau ◽  
...  
Keyword(s):  
Single Cell ◽  
Intravital Microscopy ◽  
Fusion Gene ◽  
Hypoxia Inducible Factor ◽  
Cell Lineage ◽  
Tumour Cells ◽  
Lineage Tracing ◽  
Spatially Resolved ◽  
Summary Statement

AbstractIntratumoural hypoxia is a common characteristic of malignant treatment-resistant cancers. However, hypoxia-modification strategies for the clinic remain elusive. To date little is known on the behaviour of individual hypoxic tumour cells in their microenvironment. To explore this issue in a spatial and temporally-controlled manner we developed a genetically encoded sensor by fusing the O2-labile Hypoxia-Inducible Factor 1α to eGFP and a tamoxifen-regulated Cre recombinase. Under normoxic conditions HIF-1α is degraded but under hypoxia, the HIF-1α-GFP-Cre-ERT2 fusion protein is stabilised and in the presence of tamoxifen activates a tdTomato reporter gene that is constitutively expressed in hypoxic progeny. We visualise the random distribution of hypoxic tumour cells from hypoxic or necrotic regions and vascularised areas using immunofluorescence and intravital microscopy. Once tdTomato expression is induced, it is stable for at least 4 weeks. Using this system, we could show that the post-hypoxic cells were more proliferative in vivo than non-labelled cells. Our results demonstrate that single-cell lineage tracing of hypoxic tumour cells can allow visualisation of their behaviour in living tumours using intravital microscopy. This tool should prove valuable for the study of dissemination and treatment response of post-hypoxic tumour cells in vivo at single-cell resolution.Summary StatementHere we developed and characterised a novel HIF-1α-Cre fusion gene to trace the progeny of hypoxic tumour cells in a temporal and spatially resolved manner using intravital microscopy.

scholarly journals Massively parallel single cell lineage tracing using CRISPR/Cas9 induced genetic scars

2017 ◽  
Author(s):  
Bastiaan Spanjaard ◽  
Bo Hu ◽  
Nina Mitic ◽  
Jan Philipp Junker
Keyword(s):  
Single Cell ◽  
Computational Analysis ◽  
Systematic Approach ◽  
Single Cells ◽  
Cell Lineage ◽  
Transcriptome Profiling ◽  
Cell Types ◽  
Lineage Tracing ◽  
Lineage Trees ◽  
Different Cell Types

A key goal of developmental biology is to understand how a single cell transforms into a full-grown organism consisting of many different cell types. Single-cell RNA-sequencing (scRNA-seq) has become a widely-used method due to its ability to identify all cell types in a tissue or organ in a systematic manner 1–3. However, a major challenge is to organize the resulting taxonomy of cell types into lineage trees revealing the developmental origin of cells. Here, we present a strategy for simultaneous lineage tracing and transcriptome profiling in thousands of single cells. By combining scRNA-seq with computational analysis of lineage barcodes generated by genome editing of transgenic reporter genes, we reconstruct developmental lineage trees in zebrafish larvae and adult fish. In future analyses, LINNAEUS (LINeage tracing by Nuclease-Activated Editing of Ubiquitous Sequences) can be used as a systematic approach for identifying the lineage origin of novel cell types, or of known cell types under different conditions.

scholarly journals Lymphatic system is the mainstream for breast cancer dissemination and metastasis revealed by single-cell lineage tracing

2021 ◽  
Author(s):  
Kai Miao ◽  
Aiping Zhang ◽  
Fangyuan Shao ◽  
Lijian Wang ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Lymphatic System ◽  
Expression Patterns ◽  
Cell Lineage ◽  
Tumour Cells ◽  
Lineage Tracing

Abstract Cancer metastasis is the primary cause of cancer-related death, yet the forces that drive cancer cells through various steps and different routes to distinct target organs/tissues remain elusive. In this study, we applied a CellTag system-based single-cell lineage tracing approach to show the metastasis rate and route of breast cancer cells and their interactions with the tumour microenvironment (TME) during metastasis. The results indicate that only a small fraction of cells can intravasate from the primary site into the blood circulation, whereas more cells disseminate through the lymphatic system to different organs. Tumour cells derived from the same progenitor cell exhibit different gene expression patterns in different soils, and the cancer cell-TME communication paradigm varies significantly between primary and metastatic tumours. Furthermore, metastable cells require a prewired IL-2 expression ability to migrate in vivo. In summary, leveraging a single-cell lineage tracing system, we demonstrate that the crosstalk between tumour cells and the TME is the driving force controlling the preferential metastatic fate of cancer cells through the lymphatic system and that this metastasis can be suppressed by knockdown of IL-2.

CRISPR-UMI: single-cell lineage tracing of pooled CRISPR–Cas9 screens

2017 ◽  
Vol 14 (12) ◽  
pp. 1191-1197 ◽  
Author(s):  
Georg Michlits ◽  
Maria Hubmann ◽  
Szu-Hsien Wu ◽  
Gintautas Vainorius ◽  
Elena Budusan ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Lineage ◽  
Lineage Tracing

scholarly journals Theoretical Guarantees for Phylogeny Inference from Single-Cell Lineage Tracing

2021 ◽  
Author(s):  
Robert Wang ◽  
Richard Y Zhang ◽  
Alex Khodaverdian ◽  
Nir Yosef
Keyword(s):  
Single Cell ◽  
Phylogenetic Reconstruction ◽  
Cell Lineage ◽  
Ground Truth ◽  
Lineage Tracing ◽  
Asymptotic Bounds ◽  
Exact Reconstruction ◽  
Experimental Parameters ◽  
Empirical Performance ◽  
Cutting Rate

CRISPR-Cas9 lineage tracing technologies have emerged as a powerful tool for investigating develop-ment in single-cell contexts, but exact reconstruction of the underlying clonal relationships in experiment is plagued by data-related complications. These complications are functions of the experimental parameters in these systems, such as the Cas9 cutting rate, the diversity of indel outcomes, and the rate of missing data. In this paper, we develop two theoretically grounded algorithms for reconstruction of the underlying phylogenetic tree, as well as asymptotic bounds for the number of recording sites necessary for exact recapitulation of the ground truth phylogeny at high probability. In doing so, we explore the relationship between the problem difficulty and the experimental parameters, with implications for experimental design. Lastly, we provide simulations validating these bounds and showing the empirical performance of these algorithms. Overall, this work provides a first theoretical analysis of phylogenetic reconstruction in the CRISPR-Cas9 lineage tracing technology.

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