scholarly journals Single-cell transcriptional diversity is a hallmark of developmental potential

2019 ◽  
Author(s):  
Gunsagar S. Gulati ◽  
Shaheen S. Sikandar ◽  
Daniel J. Wesche ◽  
Anoop Manjunath ◽  
Anjan Bharadwaj ◽  
...  
Keyword(s):  
Single Cell ◽  
Cellular Differentiation ◽  
Developmental Trajectories ◽  
Human Breast ◽  
Developmental Potential ◽  
Powerful Approach ◽  
Luminal Progenitor Cells ◽  
Resident Stem Cells ◽  
New Framework

AbstractSingle-cell RNA-sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. However, inferring both the state and direction of differentiation without prior knowledge has remained challenging. Here we describe a simple yet robust determinant of developmental potential—the number of detectably expressed genes per cell— and leverage this measure of transcriptional diversity to develop a new framework for predicting ordered differentiation states from scRNA-seq data. When evaluated on ~150,000 single-cell transcriptomes spanning 53 lineages and five species, our approach, called CytoTRACE, outperformed previous methods and ~19,000 molecular signatures for resolving experimentally-confirmed developmental trajectories. In addition, it enabled unbiased identification of tissue-resident stem cells, including cells with long-term regenerative potential. When used to analyze human breast tumors, we discovered candidate genes associated with less-differentiated luminal progenitor cells and validated GULP1 as a novel gene involved in tumorigenesis. Our study establishes a key RNA-based correlate of developmental potential and provides a new platform for robust delineation of cellular hierarchies (https://cytotrace.stanford.edu).

scholarly journals Single-cell transcriptional diversity is a hallmark of developmental potential

Science ◽  
2020 ◽  
Vol 367 (6476) ◽  
pp. 405-411 ◽  
Author(s):  
Gunsagar S. Gulati ◽  
Shaheen S. Sikandar ◽  
Daniel J. Wesche ◽  
Anoop Manjunath ◽  
Anjan Bharadwaj ◽  
...  
Keyword(s):  
Single Cell ◽  
Cellular Differentiation ◽  
Developmental Trajectories ◽  
Breast Tumorigenesis ◽  
Computational Framework ◽  
Developmental Potential ◽  
Gene Sets ◽  
Powerful Approach ◽  
Single Cell Rna Sequencing ◽  
Quiescent Stem Cells

Single-cell RNA sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. However, inferring both the state and direction of differentiation is challenging. Here, we demonstrate a simple, yet robust, determinant of developmental potential—the number of expressed genes per cell—and leverage this measure of transcriptional diversity to develop a computational framework (CytoTRACE) for predicting differentiation states from scRNA-seq data. When applied to diverse tissue types and organisms, CytoTRACE outperformed previous methods and nearly 19,000 annotated gene sets for resolving 52 experimentally determined developmental trajectories. Additionally, it facilitated the identification of quiescent stem cells and revealed genes that contribute to breast tumorigenesis. This study thus establishes a key RNA-based feature of developmental potential and a platform for delineation of cellular hierarchies.

scholarly journals Promoting Developmental Potential in Early Childhood: A Global Framework for Health and Education

2021 ◽  
Vol 18 (4) ◽  
pp. 2007
Author(s):  
Verónica Schiariti ◽  
Rune J. Simeonsson ◽  
Karen Hall
Keyword(s):  
Early Childhood ◽  
Developmental Trajectories ◽  
Well Being ◽  
Early Years ◽  
Early Child Development ◽  
Developmental Potential ◽  
Developmental Functioning ◽  
Global Cycles ◽  
Global Initiatives

In the early years of life, children’s interactions with the physical and social environment- including families, schools and communities—play a defining role in developmental trajectories with long-term implications for their health, well-being and earning potential as they become adults. Importantly, failing to reach their developmental potential contributes to global cycles of poverty, inequality, and social exclusion. Guided by a rights-based approach, this narrative review synthesizes selected studies and global initiatives promoting early child development and proposes a universal intervention framework of child-environment interactions to optimize children’s developmental functioning and trajectories.

scholarly journals cycleX: multi-dimensional pseudotime reveals cell cycle and differentiation relationship of dendritic cell progenitors

2017 ◽  
Author(s):  
Yong Kee Tan ◽  
Xiaomeng Zhang ◽  
Jinmiao Chen
Keyword(s):  
Cell Cycle ◽  
Dendritic Cell ◽  
Single Cell ◽  
Cellular Differentiation ◽  
Developmental Trajectories ◽  
Cellular Heterogeneity ◽  
Good Representation ◽  
Continuous Processes ◽  
Inference Methods ◽  
Relationship Of

AbstractAdvances in single-cell RNA-sequencing have helped reveal the previously underappreciated level of cellular heterogeneity present during cellular differentiation. A static snapshot of single-cell transcriptomes provides a good representation of the various stages of differentiation as differentiation is rarely synchronized between cells. Data from numerous single-cell analyses has suggested that cellular differentiation and development can be conceptualized as continuous processes. Consequently, computational algorithms have been developed to infer pseudotimes and re-ordered cells along developmental trajectories. However, existing pseudotime inference methods generate one-dimensional pseudotime in an unsupervised manner, which is inadequate to elucidate the effects of individual biological processes such as cell cycle and differentiation and the links between them. Here we present a method called cycleX which infers multi-dimensional pseudotimes to reveal putative relationship between cell cycle and differentiation during dendritic cell development. cycleX can be also applied to generate multi-dimensional pseudotime for the relationship among cell cycle, differentiation, trafficking, activation, metabolism and etc.

scholarly journals SUGAR-seq enables simultaneous detection of glycans, epitopes, and the transcriptome in single cells

2021 ◽  
Vol 7 (8) ◽  
pp. eabe3610
Author(s):  
Conor J. Kearney ◽  
Stephin J. Vervoort ◽  
Kelly M. Ramsbottom ◽  
Izabela Todorovski ◽  
Emily J. Lelliott ◽  
...  
Keyword(s):  
Single Cell ◽  
Posttranslational Modification ◽  
Cellular Differentiation ◽  
Single Cells ◽  
Simultaneous Detection ◽  
Surface Protein ◽  
Rna Seq ◽  
Cell Level ◽  
Simultaneous Integration ◽  
Unique Surface

Multimodal single-cell RNA sequencing enables the precise mapping of transcriptional and phenotypic features of cellular differentiation states but does not allow for simultaneous integration of critical posttranslational modification data. Here, we describe SUrface-protein Glycan And RNA-seq (SUGAR-seq), a method that enables detection and analysis of N-linked glycosylation, extracellular epitopes, and the transcriptome at the single-cell level. Integrated SUGAR-seq and glycoproteome analysis identified tumor-infiltrating T cells with unique surface glycan properties that report their epigenetic and functional state.

scholarly journals Adult tissue-resident stem cells—fact or fiction?

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Deepa Bhartiya
Keyword(s):  
Stem Cells ◽  
Single Cell ◽  
Adult Stem Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Tissue Specific ◽  
Cardiac Tissues ◽  
Adult Tissues ◽  
Resident Stem Cells ◽  
Abundant Cytoplasm

AbstractLife-long tissue homeostasis of adult tissues is supposedly maintained by the resident stem cells. These stem cells are quiescent in nature and rarely divide to self-renew and give rise to tissue-specific “progenitors” (lineage-restricted and tissue-committed) which divide rapidly and differentiate into tissue-specific cell types. However, it has proved difficult to isolate these quiescent stem cells as a physical entity. Recent single-cell RNAseq studies on several adult tissues including ovary, prostate, and cardiac tissues have not been able to detect stem cells. Thus, it has been postulated that adult cells dedifferentiate to stem-like state to ensure regeneration and can be defined as cells capable to replace lost cells through mitosis. This idea challenges basic paradigm of development biology regarding plasticity that a cell enters point of no return once it initiates differentiation. The underlying reason for this dilemma is that we are putting stem cells and somatic cells together while processing for various studies. Stem cells and adult mature cell types are distinct entities; stem cells are quiescent, small in size, and with minimal organelles whereas the mature cells are metabolically active and have multiple organelles lying in abundant cytoplasm. As a result, they do not pellet down together when centrifuged at 100–350g. At this speed, mature cells get collected but stem cells remain buoyant and can be pelleted by centrifuging at 1000g. Thus, inability to detect stem cells in recently published single-cell RNAseq studies is because the stem cells were unknowingly discarded while processing and were never subjected to RNAseq. This needs to be kept in mind before proposing to redefine adult stem cells.

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