Stem cell differentiation trajectories in Hydra resolved at single-cell resolution

The adult Hydra polyp continually renews all of its cells using three separate stem cell populations, but the genetic pathways enabling this homeostatic tissue maintenance are not well understood. We sequenced 24,985 Hydra single-cell transcriptomes and identified the molecular signatures of a broad spectrum of cell states, from stem cells to terminally differentiated cells. We constructed differentiation trajectories for each cell lineage and identified gene modules and putative regulators expressed along these trajectories, thus creating a comprehensive molecular map of all developmental lineages in the adult animal. In addition, we built a gene expression map of the Hydra nervous system. Our work constitutes a resource for addressing questions regarding the evolution of metazoan developmental processes and nervous system function.

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Stem cell differentiation trajectories inHydraresolved at single-cell resolution

10.1101/460154 ◽

2018 ◽

Cited By ~ 11

Author(s):

Stefan Siebert ◽

Jeffrey A. Farrell ◽

Jack F. Cazet ◽

Yashodara L. Abeykoon ◽

Abby S. Primack ◽

...

Keyword(s):

Nervous System ◽

Stem Cell ◽

Cell Differentiation ◽

Cell Lineage ◽

Stem Cell Differentiation ◽

Cell Types ◽

Differentiated Cells ◽

Nervous System Function ◽

Stem Cell Populations ◽

Molecular Description

AbstractThe adultHydrapolyp continuously renews all of its cells using three separate stem cell populations, but the genetic pathways enabling homeostatic tissue maintenance are not well understood. We used Drop-seq to sequence transcriptomes of 24,985 singleHydracells and identified the molecular signatures of a broad spectrum of cell states, from stem cells to terminally differentiated cells. We constructed differentiation trajectories for each cell lineage and identified the transcription factors expressed along these trajectories, thus creating a comprehensive molecular map of all developmental lineages in the adult animal. We unexpectedly found that neuron and gland cell differentiation transits through a common progenitor state, suggesting a shared evolutionary history for these secretory cell types. Finally, we have built the first gene expression map of theHydranervous system. By producing a comprehensive molecular description of the adultHydrapolyp, we have generated a resource for addressing fundamental questions regarding the evolution of developmental processes and nervous system function.

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The Emergent Connectome in Caenorhabditis elegans Embryogenesis

10.1101/146035 ◽

2017 ◽

Cited By ~ 1

Author(s):

◽

Bradly Alicea

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Cell Lineage ◽

Model Organism ◽

Secondary Data ◽

Building Blocks ◽

C Elegans ◽

Differentiated Cells ◽

Adult Hermaphrodite ◽

Nervous System Function

ABSTRACTThe relatively new field of connectomics provides us with a unique window into nervous system function. In the model organism Caenorhabditis elegans, this promise is even greater due to the relatively small number of cells (302) in its nervous system. While the adult C. elegans connectome has been characterized, the emergence of these networks in development has yet to be established. In this paper, we approach this problem using secondary data describing the birth times of terminally-differentiated cells as they appear in the embryo and a connectomics model for nervous system cells in the adult hermaphrodite. By combining these two sources of data, we can better understand patterns that emerge in an incipient connectome. This includes identifying at what point in embryogenesis the cells of a connectome first comes into being, potentially observing some of the earliest neuron-neuron interactions, and making comparisons between the formally-defined connectome and developmental cell lineages. An analysis is also conducted to root terminally-differentiated cells in their developmental cell lineage precursors. This reveals subnetworks with different properties at 300 minutes of embryogenesis. Additional investigations reveal the spatial position of neuronal cells born during pre-hatch development, both within and outside the connectome model, in the context of all developmental cells in the embryo. Overall, these analyses reveal important information about the birth order of specific cells in the connectome, key building blocks of global connectivity, and how these structures correspond to key events in early development.

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Using Single-Cell and Spatial Transcriptomes to Understand Stem Cell Lineage Specification During Early Embryo Development

Annual Review of Genomics and Human Genetics ◽

10.1146/annurev-genom-120219-083220 ◽

2020 ◽

Vol 21 (1) ◽

pp. 163-181

Author(s):

Guangdun Peng ◽

Guizhong Cui ◽

Jincan Ke ◽

Naihe Jing

Keyword(s):

Stem Cell ◽

Single Cell ◽

Rna Sequencing ◽

Cell Fate ◽

Cell Lineage ◽

Stem Cell Differentiation ◽

Early Embryo ◽

Stem Cell Lineage ◽

Single Cell Rna Sequencing ◽

Cell Organization

Embryonic development and stem cell differentiation provide a paradigm to understand the molecular regulation of coordinated cell fate determination and the architecture of tissue patterning. Emerging technologies such as single-cell RNA sequencing and spatial transcriptomics are opening new avenues to dissect cell organization, the divergence of morphological and molecular properties, and lineage allocation. Rapid advances in experimental and computational tools have enabled researchers to make many discoveries and revisit old hypotheses. In this review, we describe the use of single-cell RNA sequencing in studies of molecular trajectories and gene regulation networks for stem cell lineages, while highlighting the integratedexperimental and computational analysis of single-cell and spatial transcriptomes in the molecular annotation of tissue lineages and development during postimplantation gastrulation.

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Faculty Opinions recommendation of Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1022101.251696 ◽

2004 ◽

Author(s):

Magdalena Goetz

Keyword(s):

Nervous System ◽

Stem Cell ◽

Cell Differentiation ◽

Neural Stem Cell ◽

Stem Cell Differentiation

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Transformative opportunities for single-cell proteomics

10.7287/peerj.preprints.26821v2 ◽

2018 ◽

Cited By ~ 1

Author(s):

Harrison Specht ◽

Nikolai Slavov

Keyword(s):

Mass Spectrometry ◽

Stem Cell ◽

Cell Differentiation ◽

Single Cell ◽

Single Cells ◽

Biological Systems ◽

Stem Cell Differentiation ◽

New Age ◽

Technological Developments

Many pressing medical challenges - such as diagnosing disease, enhancing directed stem cell differentiation, and classifying cancers - have long been hindered by limitations in our ability to quantify proteins in single cells. Mass-spectrometry (MS) is poised to transcend these limitations by developing powerful methods to routinely quantify thousands of proteins and proteoforms across many thousands of single cells. We outline specific technological developments and ideas that can increase the sensitivity and throughput of single cell MS by orders of magnitude and usher in this new age. These advances will transform medicine and ultimately contribute to understanding biological systems on an entirely new level.

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Enteric Nervous System Regulation of Intestinal Stem Cell Differentiation and Epithelial Monolayer Function

Scientific Reports ◽

10.1038/s41598-018-24768-3 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 28

Author(s):

Marissa Puzan ◽

Sanjin Hosic ◽

Caroline Ghio ◽

Abigail Koppes

Keyword(s):

Nervous System ◽

Stem Cell ◽

Cell Differentiation ◽

Enteric Nervous System ◽

Stem Cell Differentiation ◽

Intestinal Stem Cell ◽

Epithelial Monolayer

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

Cell Cycle ◽

10.4161/cc.9.8.11252 ◽

2010 ◽

Vol 9 (8) ◽

pp. 1504-1510 ◽

Cited By ~ 26

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

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Endogenous stem cell proliferation after central nervous system injury: alternative therapeutic options

Neurosurgical FOCUS ◽

10.3171/foc.2005.19.3.2 ◽

2005 ◽

Vol 19 (3) ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Nicholas C. Bambakidis ◽

Nicholas Theodore ◽

Peter Nakaji ◽

Adrian Harvey ◽

Volker K. H. Sonntag ◽

...

Keyword(s):

Central Nervous System ◽

Cell Proliferation ◽

Nervous System ◽

Stem Cell ◽

Neurological Diseases ◽

Cell Populations ◽

Stem Cell Proliferation ◽

Cord Injury ◽

Stem Cell Populations ◽

Endogenous Stem Cell

The continuous regeneration of glial cells arising from endogenous stem cell populations in the central nervous system (CNS) occurs throughout life in mammals. In the ongoing research to apply stem cell therapy to neurological diseases, the capacity to harness the multipotential ability of endogenous stem cell populations has become apparent. Such cell populations proliferate in response to a variety of injury states in the CNS, but in the absence of a supportive microenvironment they contribute little to any significant behavioral recovery. In the authors' laboratory and elsewhere, recent research on the regenerative potential of these stem cells in disease states such as spinal cord injury has demonstrated that the cells' proliferative potential may be greatly upregulated in response to appropriate growth signals and exogenously applied trophic factors. Further understanding of the potential of such multipotent cells and the mechanisms responsible for creating a favorable microenvironment for them may lead to additional therapeutic alternatives in the setting of neurological diseases. These therapies would require no exogenous stem cell sources and thus would avoid the ethical and moral considerations regarding their use. In this review the authors provide a brief overview of the enhancement of endogenous stem cell proliferation following neurological insult.

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