scholarly journals Revealing Dynamic Mechanisms of Cell Fate Decisions From Single-Cell Transcriptomic Data

2019 ◽  
Vol 10 ◽  
Author(s):  
Jiajun Zhang ◽  
Qing Nie ◽  
Tianshou Zhou
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Cell Fate Decisions ◽  
Transcriptomic Data ◽  
Dynamic Mechanisms

scholarly journals Topographer Reveals Dynamic Mechanisms of Cell Fate Decisions from Single-Cell Transcriptomic Data

2018 ◽  
Author(s):  
Jiajun Zhang ◽  
Qing Nie ◽  
Tianshou Zhou
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Branch Point ◽  
State Transition ◽  
Transition Probabilities ◽  
Marker Gene ◽  
Complex Cell ◽  
Cell Fate Decisions ◽  
Transcriptomic Data ◽  
Cell State

AbstractCell fate decisions play a pivotal role in development but technologies for dissecting them are limited. We developed a multifunction new method, Topographer to construct a ‘quantitative’ Waddington’s landscape of single-cell transcriptomic data. This method is able to identify complex cell-state transition trajectories and to estimate complex cell-type dynamics characterized by fate and transition probabilities. It also infers both marker gene networks and their dynamic changes as well as dynamic characteristics of transcriptional bursting along the cell-state transition trajectories. Applying this method to single-cell RNA-seq data on the differentiation of primary human myoblasts, we not only identified three known cell types but also estimated both their fate probabilities and transition probabilities among them. We found that the percent of genes expressed in a bursty manner is significantly higher at (or near) the branch point (∼97%) than before or after branch (below 80%), and that both gene-gene and cell-cell correlation degrees are apparently lower near the branch point than away from the branching. Topographer allows revealing of cell fate mechanisms in a coherent way at three scales: cell lineage (macroscopic), gene network (mesoscopic) and gene expression (microscopic).

scholarly journals Resolution of Cell Fate Decisions Revealed by Single-Cell Gene Expression Analysis from Zygote to Blastocyst

2010 ◽  
Vol 18 (4) ◽  
pp. 675-685 ◽  
Author(s):  
Guoji Guo ◽  
Mikael Huss ◽  
Guo Qing Tong ◽  
Chaoyang Wang ◽  
Li Li Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Cell Fate ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Cell Fate Decisions ◽  
Cell Gene Expression ◽  
Cell Gene

scholarly journals Single-cell transcriptional analysis to uncover regulatory circuits driving cell fate decisions in early mouse development

2014 ◽  
Vol 31 (7) ◽  
pp. 1060-1066 ◽  
Author(s):  
Haifen Chen ◽  
Jing Guo ◽  
Shital K. Mishra ◽  
Paul Robson ◽  
Mahesan Niranjan ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Transcriptional Analysis ◽  
Mouse Development ◽  
Cell Fate Decisions ◽  
Regulatory Circuits ◽  
Early Mouse

scholarly journals Basal stem cell fate specification is mediated by SMAD signaling in the developing human lung

2018 ◽  
Author(s):  
Alyssa J. Miller ◽  
Qianhui Yu ◽  
Michael Czerwinski ◽  
Yu-Hwai Tsai ◽  
Renee F. Conway ◽  
...  
Keyword(s):  
Single Cell ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Basal Cell ◽  
Human Lung ◽  
Branching Morphogenesis ◽  
Basal Cells ◽  
Smad Signaling ◽  
Cell Fate Decisions ◽  
Cell Transition

AbstractBasal stem cells (basal cells), located in the bronchi and trachea of the human lung epithelium, play a critical role in normal airway homeostasis and repair, and have been implicated in the development of diseases such as cancer1-4. Additionally, basal-like cells contribute to alveolar regeneration and fibrosis following severe injury5-8. However, the developmental origin of basal cells in humans is unclear. Previous work has shown that specialized progenitor cells exist at the tips of epithelial tubes during lung branching morphogenesis, and in mice, give rise to all alveolar and airway lineages9,10. These ‘bud tip progenitor cells’ have also been described in the developing human lung11-13, but the mechanisms controlling bud tip differentiation into specific cell lineages, including basal cells, are unknown. Here, we interrogated the bud tip-to-basal cell transition using human tissue specimens, bud tip progenitor organoid cultures11, and single-cell transcriptomics. We used single-cell mRNA sequencing (scRNAseq) of developing human lung specimens from 15-21 weeks gestation to identify molecular signatures and cell states in the developing human airway epithelium. We then inferred differentiation trajectories during bud tip-to-airway differentiation, which revealed a previously undescribed transitional cell state (‘hub progenitors’) and implicated SMAD signaling as a regulator of the bud tip-to-basal cell transition. We used bud tip progenitor organoids to show that TGFT1 and BMP4 mediated SMAD signaling robustly induced the transition into functional basal-like cells, and these in vitro-derived basal cells exhibited clonal expansion, self-renewal and multilineage differentiation. This work provides a framework for deducing and validating key regulators of cell fate decisions using single cell transcriptomics and human organoid models. Further, the identification of SMAD signaling as a critical regulator of newly born basal cells in the lung may have implications for regenerative medicine, basal cell development in other organs, and understanding basal cell misregulation in disease.

Abstract 39: Fate Of Renin Cell Progenitors In The Developing Kidney Vasculature

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Alexandre Martini ◽  
Ariel R Gomez ◽  
Maria Luisa Sequeira Lopez
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Fluorescent Protein ◽  
Enrichment Analysis ◽  
Cell Fate Decisions ◽  
Mural Cells ◽  
Developing Kidney ◽  
Green Fluorescent ◽  
Old Mice ◽  
Accessible Chromatin

The unique spatial arregement of the kidney arterioles is an essential event for its development. However, the mechanisms that govern this process are still poorly understood. During nephrogenesis, a group of stromal cells expressing the Forkhead Box D1 ( FoxD1 ) transcription factor (TF) will give rise to the metanephric progenitors for the mural cells of the kidneys arteries and arterioles. We aim to identify the core TFs involved in the cell fate along the differentiaton pathways of the developing kidney vasculature. Therefore, we generated Foxd1-cre; mTmG mice, whose Foxd1 derivative cells are labeled with green fluorescent protein (GFP). GFP+ cells were isolated from 5 (P5) or 30 (P30) days old mice kidneys, and processed either for single-cell RNA-Seq (scRNA-Seq) or for single-cell Assay for Transposase-Accessible Chromatin (scATAC-Seq ). The top5 highly expressed TFs on scRNA-Seq at P5 are: Tcf21, Zeb2, Meis2, Cebpd and Nme3 (p_adjusted_value(padj)= 0, 3.8E-187, 3.9E-180, 4E-172, 4.1E-172 and 3.2E-154, respectively). They are involved in developmental processes and cell proliferation. At P30, the top5 highly expressed TFs are: Atf3, klf2, Fos, Nr4a2 and Junb (padj= 4.2E-294, 2.1E-200, 3.5E-182, 1.7E-52 and 0.2E-24, respectively). They are implicated with calcium-signaling pathway and inflammation. Additionally, scATAC-Seq identifies regions of accessible chromatin for pontential TFs binding, leading to changes in gene expression content and cell identity. At P30, scATAC-Seq showed differential accessible regions with subsequent putative motif enrichment analysis for the TF N4a2 (padj: 4E-297). This is in accordance with our scRNA-Seq results and might play a role in the Foxd1 progenitors cell fate decisions. Our results tracks the fate of the Foxd1+ cells during the kidney vasculature assembly and suggest a new transcription factors network that might play a role to orchestrate cell fate decisions during kidney vascular development.

scholarly journals Resolving Cell Fate Decisions during Somatic Cell Reprogramming by Single-Cell RNA-Seq

2019 ◽  
Vol 73 (4) ◽  
pp. 815-829.e7 ◽  
Author(s):  
Lin Guo ◽  
Lihui Lin ◽  
Xiaoshan Wang ◽  
Mingwei Gao ◽  
Shangtao Cao ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Single Cell ◽  
Cell Fate ◽  
Cell Reprogramming ◽  
Rna Seq ◽  
Cell Fate Decisions ◽  
Somatic Cell Reprogramming

Single Cell RNA seq for Analysis of Cell Fate Decisions

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-20-SCI-20
Author(s):  
H. Leighton Grimes ◽  
Singh Harinder ◽  
Andre Olsson ◽  
Nathan Salomonis ◽  
Bruce J. Aronow ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Fate ◽  
Clustering Analysis ◽  
Conflicts Of Interest ◽  
Regulatory Gene ◽  
Rna Seq ◽  
Regulatory State ◽  
Cell Fate Decisions ◽  
General Utility ◽  
Developmental Hierarchy

Abstract Single-cell RNA-Seq has the potential to become a dominant approach in probing diverse and complex developmental compartments. Its unbiased and comprehensive nature could enable developmental ordering of cellular and regulatory gene hierarchies without prior knowledge. To test general utility we performed single-cell RNA-seq of murine hematopoietic progenitors focusing on the myeloid developmental hierarchy. Using novel unsupervised clustering analysis, ICDS, we correctly ordered known hierarchical states as well as revealed rare intermediates. Regulatory state analysis suggested that the transcription factors Gfi1 and Irf8 function antagonistically to control homeostatic neutrophil and macrophage production, respectively. This prediction was validated by complementary genetic and genomic experiments in granulocyte-macrophage progenitors. Using knock-in reporters for Gfi1 and Irf8 and clonogenic analyses coupled with single-cell RNA-seq we distinguished regulatory states of bi-potential progenitors from their lineage specifying or committed progeny. Thus single-cell RNA-Seq is a powerful developmental tool to characterize hierarchical and rare cellular states along with the regulators that control their dynamics. Disclosures No relevant conflicts of interest to declare.

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