scholarly journals Dynamic spatiotemporal coordination of neural stem cell fate decisions through local feedback in the adult vertebrate brain

2020 ◽  
Author(s):  
Nicolas Dray ◽  
Laure Mancini ◽  
Udi Binshtok ◽  
Felix Cheysson ◽  
Willy Supatto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Life Time ◽  
Population Level ◽  
Dynamic Imaging ◽  
Cell Fate Decisions ◽  
Vertebrate Brain ◽  
And Control

SUMMARYNeural stem cell (NSC) populations persist in the adult vertebrate brain over a life time, and their homeostasis is controlled at the population level. The nature and properties of these coordination mechanisms remain unknown. Here we combine dynamic imaging of entire NSC populations in their in vivo niche over weeks, pharmacological manipulations, mathematical modeling and spatial statistics, and demonstrate that NSCs use spatiotemporally resolved local feedbacks to coordinate their decision to divide. These involve a Notch-mediated inhibition from transient neural progenitors, and a dispersion effect from dividing NSCs themselves, exerted with a delay of 9-12 days. Simulations from a stochastic NSC lattice model capturing these interactions demonstrate that they are linked by lineage progression and control the spatiotemporal distribution of output neurons. These results highlight how local and temporally delayed interactions occurring between brain germinal cells generate self-propagating dynamics that maintain NSC population homeostasis with specific spatiotemporal correlations.

Histone crotonylation regulates neural stem cell fate decisions by activating bivalent promoters

EMBO Reports ◽  
2021 ◽  
Author(s):  
Shang‐Kun Dai ◽  
Pei‐Pei Liu ◽  
Hong‐Zhen Du ◽  
Xiao Liu ◽  
Ya‐Jie Xu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Stem Cell Fate ◽  
Cell Fate Decisions

scholarly journals Encapsulation and recovery of murine hematopoietic stem and progenitor cells in a thiol-crosslinked maleimide-functionalized gelatin hydrogel

2021 ◽  
Author(s):  
Aidan E Gilchrist ◽  
Julio F. Serrano ◽  
Mai T. Ngo ◽  
Zona Hrnjak ◽  
Sanha Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Click Reaction ◽  
Uv Light ◽  
3D Culture ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions

Biomaterial platforms are an integral part of stem cell biomanufacturing protocols. The collective biophysical, biochemical, and cellular cues of the stem cell niche microenvironment play an important role in regulating stem cell fate decisions. Three-dimensional (3D) culture of stem cells within biomaterials provides a route to present biophysical and biochemical stimuli such as cell-matrix interactions and cell-cell interactions via secreted biomolecules. Herein, we describe a maleimide-functionalized gelatin (GelMAL) hydrogel that can be crosslinked via thiol-Michael addition click reaction for the encapsulation of sensitive stem cell populations. The maleimide functional units along the gelatin backbone enables gelation via the addition of a dithiol crosslinker without requiring external stimuli (e.g., UV light, photoinitiator), reducing reactive oxide species generation. Additionally, the versatility of crosslinker selection enables easy insertion of thiol-containing bioactive or bioinert motifs. Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) were encapsulated in GelMAL, with mechanical properties tuned to mimic the in vivo bone marrow niche. We report insertion of a cleavable peptide crosslinker that can be degraded by the proteolytic action of SortaseA, a mammalian-inert enzyme. Notably, SortaseA exposure preserves stem cell surface markers, an essential metric of hematopoietic activity used in immunophenotyping. This novel GelMAL system enables a route to producing artificial stem cell niches with tunable biophysical properties with intrinsic cell-interaction motifs and orthogonal addition of bioactive crosslinks.

scholarly journals Modulated DISP3/PTCHD2 expression influences neural stem cell fate decisions

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jana Konířová ◽  
Jana Oltová ◽  
Alicia Corlett ◽  
Justyna Kopycińska ◽  
Michal Kolář ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Stem Cell Fate ◽  
Cell Fate Decisions

scholarly journals Vascular Regulation of Hematopoietic Stem Cell Homeostasis, Regeneration, and Aging

2021 ◽  
Author(s):  
Pradeep Ramalingam ◽  
Jason M. Butler ◽  
Michael G. Poulos
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Dynamic Imaging ◽  
Model Systems ◽  
Hematopoietic Stem ◽  
Perivascular Cell ◽  
Cell Fate Decisions ◽  
Vascular Regulation

Abstract Purpose of Review Hematopoietic stem cells (HSCs) sit at the top of the hierarchy that meets the daily burden of blood production. HSC maintenance relies on extrinsic cues from the bone marrow (BM) microenvironment to balance stem cell self-renewal and cell fate decisions. In this brief review, we will highlight the studies and model systems that define the centralized role of BM vascular endothelium in modulating HSC activity in health and stress. Recent Findings The BM microenvironment is composed of a diverse array of intimately associated vascular and perivascular cell types. Recent dynamic imaging studies, coupled with single-cell RNA sequencing (scRNA-seq) and functional readouts, have advanced our understanding of the HSC-supportive cell types and their cooperative mechanisms that govern stem cell fate during homeostasis, regeneration, and aging. These findings have established complex and discrete vascular microenvironments within the BM that express overlapping and unique paracrine signals that modulate HSC fate. Summary Understanding the spatial and reciprocal HSC-niche interactions and the molecular mechanisms that govern HSC activity in the BM vascular microenvironment will be integral in developing therapies aimed at ameliorating hematological disease and supporting healthy hematopoietic output.

scholarly journals Mitochondrial Control of Stem Cell State and Fate: Lessons From Drosophila

2021 ◽  
Vol 9 ◽  
Author(s):  
Satish Kumar Tiwari ◽  
Sudip Mandal
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Types ◽  
Extrinsic Factors ◽  
Cell Fate Decisions ◽  
Cell State ◽  
Resident Stem Cells ◽  
Stem Cell State

Over the years, Drosophila has served as a wonderful genetically tractable model system to unravel various facets of tissue-resident stem cells in their microenvironment. Studies in different stem and progenitor cell types of Drosophila have led to the discovery of cell-intrinsic and extrinsic factors crucial for stem cell state and fate. Though initially touted as the ATP generating machines for carrying various cellular processes, it is now increasingly becoming clear that mitochondrial processes alone can override the cellular program of stem cells. The last few years have witnessed a surge in our understanding of mitochondria’s contribution to governing different stem cell properties in their subtissular niches in Drosophila. Through this review, we intend to sum up and highlight the outcome of these in vivo studies that implicate mitochondria as a central regulator of stem cell fate decisions; to find the commonalities and uniqueness associated with these regulatory mechanisms.

scholarly journals Differential Network Analysis Reveals Regulatory Patterns in Neural Stem Cell Fate Decision

2019 ◽  
Author(s):  
Jiang Xie ◽  
Fuzhang yang ◽  
Jiamin Sun ◽  
Jiao Wang
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Integrative Analysis ◽  
Cell Fate Decisions ◽  
Multi Stage ◽  
Gene Regulatory ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Background Neural stem cell (NSC) differentiation is one of many multi-stage lineage systems that require multiple cell fate decisions. Recent single-cell transcriptome datasets became available at individual differentiation, however, a systematic and integrative analysis of multiple datasets at multiple temporal points of NSC differentiation is lacking. Results Here we investigate five NSC differentiation paths by analyzing and comparing four different single-cell transcriptome datasets. By constructing gene regulatory networks for each cell type, we delineate their regulatory patterns via analyses of differential topology and network diffusion. Among the five NSC differentiation paths, we find 12 common differentially expressed genes, with one common three-gene regulatory pattern shared by all paths. The identified regulatory pattern, partly supported by previous experimental evidence, is found to be essential to all differentiation paths, however, plays a different role in each path when regulating other genes. Conclusions Together, our integrative analysis provides both common and specific regulatory mechanisms for each of the five NSC differentiation paths, and the approach can be applied to analyzing other complex multi-stage lineage systems.

scholarly journals Mechanical Compression Creates a Quiescent Muscle Stem Cell Niche

2021 ◽  
Author(s):  
Jiaxiang Tao ◽  
Mohammad Ikbal Choudhury ◽  
Debonil Maity ◽  
Taeki Kim ◽  
Sean Sun ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Life Time ◽  
Apical Surface ◽  
Muscle Stem Cells ◽  
Cell Niche ◽  
Edge Tension ◽  
Stem Cell State

Skeletal muscles can regenerate throughout life time from resident Pax7-expressing (Pax7+) muscle stem cells (MuSCs). Pax7+ MuSCs are normally quiescent and localized at a niche in which they are attached to the extracellular matrix basally and compressed against the myofiber apically. Upon muscle injury, MuSCs lose apical contact with the myofiber and re-enter cell cycle to initiate regeneration. Prior studies on the physical niche of MuSCs focused on basal elasticity, and significance of the apical force exerted on MuSCs remains unaddressed. Here we simulate MuSCs' mechanical environment in vivo by applying physical compression to MuSCs' apical surface. We demonstrate that compression drives activated MuSCs back to a quiescent stem cell state, even when seeded on different basal elasticities. By mathematical modeling and manipulating cell tension, we conclude that low overall tension combined with high edge tension generated by compression lead to MuSC quiescence. We further show that apical compression results in up-regulation of Notch downstream genes, accompanied by increased levels of nuclear Notch. The compression-induced nuclear Notch is ligand-independent, as it does not require the canonical S2-cleavage of Notch by ADAM10/17. Our results fill the knowledge gap on the role of apical tension for MuSC fate. Implications to how stem cell fate and activity are interlocked with the mechanical integrity of its resident tissue are discussed.

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