Abstract 939: Single cell mRNA expression profiling reveals heterogeneity of normal and malignant breast stem cell populations

ABSTRACTHow stem cells give rise to human interfollicular epidermis is unclear despite the crucial role the epidermis plays in barrier and appendage formation. Here we use single cell-RNA sequencing to interrogate basal stem cell heterogeneity of human interfollicular epidermis and find at least four spatially distinct stem cell populations that decorate the top and bottom of rete ridge architecture and hold transitional positions between the basal and suprabasal epidermal layers. Cell-cell communication modeling through co-variance of cognate ligand-receptor pairs indicate that the basal cell populations distinctly serve as critical signaling hubs that maintain epidermal communication. Combining pseudotime, RNA velocity, and cellular entropy analyses point to a hierarchical differentiation lineage supporting multi-stem cell interfollicular epidermal homeostasis models and suggest the “transitional” basal stem cells are stable states essential for proper stratification. Finally, alterations in differentially expressed “transitional” basal stem cell genes result in severe thinning of human skin equivalents, validating their essential role in epidermal homeostasis and reinforcing the critical nature of basal stem cell heterogeneity.

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Direct confirmation of quiescence of CD34+CD38- leukemia stem cell populations using single cell culture, their molecular signature and clinicopathological implications

BMC Cancer ◽

10.1186/s12885-015-1233-x ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 10

Author(s):

Eun Jeong Won ◽

Hye-Ran Kim ◽

Ra-Young Park ◽

Seok-Yong Choi ◽

Jong Hee Shin ◽

...

Keyword(s):

Cell Culture ◽

Stem Cell ◽

Single Cell ◽

Molecular Signature ◽

Cell Populations ◽

Leukemia Stem Cell ◽

Single Cell Culture ◽

Stem Cell Populations ◽

Direct Confirmation

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A reference single-cell transcriptomic atlas of human skeletal muscle tissue reveals bifurcated muscle stem cell populations

Skeletal Muscle ◽

10.1186/s13395-020-00236-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Andrea J. De Micheli ◽

Jason A. Spector ◽

Olivier Elemento ◽

Benjamin D. Cosgrove

Keyword(s):

Skeletal Muscle ◽

Stem Cell ◽

Single Cell ◽

Muscle Tissue ◽

Human Skeletal Muscle ◽

Skeletal Muscle Tissue ◽

Cell Populations ◽

Muscle Stem Cell ◽

Stem Cell Populations

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Designing signaling environments to steer transcriptional diversity in neural progenitor cell populations

10.1101/2019.12.30.890087 ◽

2019 ◽

Author(s):

Jong H. Park ◽

Tiffany Tsou ◽

Paul Rivaud ◽

Matt Thomson ◽

Sisi Chen

Keyword(s):

Cell Culture ◽

Population Structure ◽

Stem Cell ◽

Single Cell ◽

Neural Stem Cell ◽

Cell Populations ◽

List Type ◽

Developmental Potential ◽

Stem Cell Populations

AbstractStem cell populations within developing embryos are diverse, composed of many different sub-populations of cells with varying developmental potential. The structure of stem cell populations in cell culture remains poorly understood and presents a barrier to differentiating stem cells for therapeutic applications. In this paper we develop a framework for controlling the architecture of stem cell populations in cell culture using high-throughput single cell mRNA-seq and computational analysis. We find that the transcriptional diversity of neural stem cell populations collapses in cell culture. Cell populations are depleted of committed neuron progenitor cells and become dominated by a single pre-astrocytic cell population. By analyzing the response of neural stem cell populations to forty distinct signaling conditions, we demonstrate that signaling environments can restructure cell populations by modulating the relative abundance of pre-astrocyte and pre-neuron subpopulations according to a simple linear code. One specific combination of BMP4, EGF, and FGF2 ligands switches the default population balance such that 70% of cells correspond to the committed neurons. Our work demonstrates that single-cell RNA-seq can be applied to modulate the diversity of in vitro stem cell populations providing a new strategy for population-level stem cell control.HighlightsNatural progenitor diversity in the brain collapses during in vitro culture to a single progenitor typeLoss of progenitor diversity alters fate potential of cells during differentiationLarge scale single-cell signaling screen identifies signals that reshape population structure towards neuronal cell typesSignals regulate population structure according to a simple log-linear model

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High-Resolution Microfluidic Single-Cell Transcriptional Profiling Reveals Clinically Relevant Subtypes among Human Stem Cell Populations Commonly Utilized in Cell-Based Therapies

Frontiers in Neurology ◽

10.3389/fneur.2016.00041 ◽

2016 ◽

Vol 7 ◽

Cited By ~ 5

Author(s):

Robert C. Rennert ◽

Richard Schäfer ◽

Tonya Bliss ◽

Michael Januszyk ◽

Michael Sorkin ◽

...

Keyword(s):

Stem Cell ◽

High Resolution ◽

Single Cell ◽

Transcriptional Profiling ◽

Cell Populations ◽

Human Stem Cell ◽

Stem Cell Populations

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A single cell atlas of human teeth

10.1101/2021.02.19.431962 ◽

2021 ◽

Author(s):

Pierfrancesco Pagella ◽

Laura de Vargas Roditi ◽

Bernd Stadlinger ◽

Andreas E. Moor ◽

Thimios A. Mitsiadis

Keyword(s):

Stem Cell ◽

Single Cell ◽

Cellular Heterogeneity ◽

Cell Populations ◽

Therapeutic Approaches ◽

Human Teeth ◽

Functional Differences ◽

Potential Source ◽

Stem Cell Populations ◽

Transcriptional Landscape

Teeth exert fundamental functions related to mastication and speech. Despite their great biomedical importance, an overall picture of their cellular and molecular composition is still missing. In this study, we have mapped the transcriptional landscape of the various cell populations that compose human teeth at single-cell resolution, and we analyzed in deeper detail their stem cell populations and their microenvironment. Our study identified great cellular heterogeneity in the dental pulp and the periodontium. Unexpectedly, we found that the molecular signatures of the stem cell populations were very similar, and that their distinctive behavior could be due to substantial differences between their microenvironments. Our findings suggest that the microenvironmental specificity is the potential source for the major functional differences of the stem cells located in the various tooth compartments and open new perspectives towards cell-based dental therapeutic approaches.

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