scholarly journals Stem cell differentiation trajectories inHydraresolved at single-cell resolution

2018 ◽  
Author(s):  
Stefan Siebert ◽  
Jeffrey A. Farrell ◽  
Jack F. Cazet ◽  
Yashodara L. Abeykoon ◽  
Abby S. Primack ◽  
...  

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.

Science ◽  
2019 ◽  
Vol 365 (6451) ◽  
pp. eaav9314 ◽  
Author(s):  
Stefan Siebert ◽  
Jeffrey A. Farrell ◽  
Jack F. Cazet ◽  
Yashodara Abeykoon ◽  
Abby S. Primack ◽  
...  

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.


2006 ◽  
Vol 951 ◽  
Author(s):  
Batur Ercan ◽  
Thomas Webster

ABSTRACTStem cells are the source of all differentiated cells in the body. However, the stimuli that control stem cell differentiation into other cell types is still not well understood. In order to investigate this, novel carbon nanotubes (CNT's) were synthesized on anodized titanium substrates by chemical vapor deposition. Human mesenchymal stem cell (HMCS) adhesion was investigated on this nano-structured surface. The results showed significant evidence for the enhancement of HMSC adhesion on carbon nanotubes with respect to the template they were synthesized on, specifically, anodized titanium. Such evidence provides promise for the use of carbon nanotubes grown from anodized titanium to serve as novel stem cell differentiation devices.


Author(s):  
Kazuhiko Ishihara ◽  
Miu Kaneyasu ◽  
Kyoko Fukazawa ◽  
Ren Zhang ◽  
Yuji Teramura

The effects of differentiated cells on stem cell differentiation were analyzed by co-culture using a cell-encapsulated double-layered hydrogel system. As a polymer hydrogel matrix, a water-soluble zwitterionic polymer having both...


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Gabriel N Aughey ◽  
Alicia Estacio Gomez ◽  
Jamie Thomson ◽  
Hang Yin ◽  
Tony D Southall

During development eukaryotic gene expression is coordinated by dynamic changes in chromatin structure. Measurements of accessible chromatin are used extensively to identify genomic regulatory elements. Whilst chromatin landscapes of pluripotent stem cells are well characterised, chromatin accessibility changes in the development of somatic lineages are not well defined. Here we show that cell-specific chromatin accessibility data can be produced via ectopic expression of E. coli Dam methylase in vivo, without the requirement for cell-sorting (CATaDa). We have profiled chromatin accessibility in individual cell-types of Drosophila neural and midgut lineages. Functional cell-type-specific enhancers were identified, as well as novel motifs enriched at different stages of development. Finally, we show global changes in the accessibility of chromatin between stem-cells and their differentiated progeny. Our results demonstrate the dynamic nature of chromatin accessibility in somatic tissues during stem cell differentiation and provide a novel approach to understanding gene regulatory mechanisms underlying development.


Reproduction ◽  
2013 ◽  
Vol 145 (5) ◽  
pp. R139-R155 ◽  
Author(s):  
D A Rappolee ◽  
S Zhou ◽  
E E Puscheck ◽  
Y Xie

Development can happen in one of two ways. Cells performing a necessary function can differentiate from stem cells before the need for it arises and stress does not develop. Or need arises before function, stress develops and stress signals are part of the normal stimuli that regulate developmental mechanisms. These mechanisms adjust stem cell differentiation to produce function in a timely and proportional manner. In this review, we will interpret data from studies of null lethal mutants for placental stress genes that suggest the latter possibility. Acknowledged stress pathways participate in stress-induced and -regulated differentiation in two ways. These pathways manage the homeostatic response to maintain stem cells during the stress. Stress pathways also direct stem cell differentiation to increase the first essential lineage and suppress later lineages when stem cell accumulation is diminished. This stress-induced differentiation maintains the conceptus during stress. Pathogenic outcomes arise because population sizes of normal stem cells are first depleted by decreased accumulation. The fraction of stem cells is further decreased by differentiation that is induced to compensate for smaller stem cell populations. Analysis of placental lethal null mutant genes known to mediate stress responses suggests that the labyrinthine placenta develops during, and is regulated by, hypoxic stress.


2011 ◽  
Vol 39 (1) ◽  
pp. 383-387 ◽  
Author(s):  
Raymond A.A. Smith ◽  
Kate Meade ◽  
Claire E. Pickford ◽  
Rebecca J. Holley ◽  
Catherine L.R. Merry

ES (embryonic stem) cell differentiation is dependent on the presence of HS (heparan sulfate). We have demonstrated that, during differentiation, the evolution of specific cell lineages is associated with particular patterns of GAG (glycosaminoglycan) expression. For example, different HS epitopes are synthesized during neural or mesodermal lineage formation. Cell lines mutant for various components of the HS biosynthetic pathway are selectively impaired in their differentiation, with lineage-specific effects observed for some lines. We have also observed that the addition of soluble GAG saccharides to cells, with or without cell-surface HS, can influence the pace and outcome of differentiation, again highlighting specific pattern requirements for particular lineages. We are combining this work with ongoing studies into the design of artificial cell environments where we have optimized three-dimensional scaffolds, generated by electrospinning or by the formation of hydrogels, for the culture of ES cells. By permeating these scaffolds with defined GAG oligosaccharides, we intend to control the mechanical environment of the cells (via the scaffold architecture) as well as their biological signalling environment (using the oligosaccharides). We predict that this will allow us to control ES cell pluripotency and differentiation in a three-dimensional setting, allowing the generation of differentiated cell types for use in drug discovery/testing or in therapeutics.


Cells ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 114 ◽  
Author(s):  
Camilla Paoletti ◽  
Carla Divieto ◽  
Valeria Chiono

The irreversible loss of functional cardiomyocytes (CMs) after myocardial infarction (MI) represents one major barrier to heart regeneration and functional recovery. The combination of different cell sources and different biomaterials have been investigated to generate CMs by differentiation or reprogramming approaches although at low efficiency. This critical review article discusses the role of biomaterial platforms integrating biochemical instructive cues as a tool for the effective generation of functional CMs. The report firstly introduces MI and the main cardiac regenerative medicine strategies under investigation. Then, it describes the main stem cell populations and indirect and direct reprogramming approaches for cardiac regenerative medicine. A third section discusses the main techniques for the characterization of stem cell differentiation and fibroblast reprogramming into CMs. Another section describes the main biomaterials investigated for stem cell differentiation and fibroblast reprogramming into CMs. Finally, a critical analysis of the scientific literature is presented for an efficient generation of functional CMs. The authors underline the need for biomimetic, reproducible and scalable biomaterial platforms and their integration with external physical stimuli in controlled culture microenvironments for the generation of functional CMs.


2017 ◽  
Author(s):  
◽  
Bradly Alicea

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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