The effect of (prenatal) smoke exposure on lung progenitor cell behavior and Cyp2a5 gene regulation

SUMMARYRadial glial progenitors (RGPs) are responsible for producing the vast majority of neurons and glia in the neocortex. While RGP behavior and progressive generation of neocortical neurons have been delineated, the exact process of neocortical gliogenesis remains elusive. Here, we report the precise progenitor cell behavior and gliogenesis program at single-cell resolution in the mouse neocortex. RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of 60%:15%:25%, respectively, via fate-restricted “intermediate” precursor cells. While the total number of precursor cells generated by individual RGPs appears stochastic, the output of individual precursor cells exhibit clear patterns in number and subtype, and form discrete local subclusters. Clonal loss of tumor suppressor Neurofibromatosis type 1 leads to excessive production of glia selectively, especially oligodendrocyte precursor cells. These results delineate the cellular program of neocortical gliogenesis quantitatively and suggest the cellular and lineage origin of primary brain tumor.

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Chemo-Mechanical Cues Modulate Nano-Scale Chromatin Organization in Healthy and Diseased Connective Tissue Cells

10.1101/2021.04.27.441596 ◽

2021 ◽

Author(s):

Su-Jin Heo ◽

Shreyasi Thakur ◽

Xingyu Chen ◽

Claudia Loebel ◽

Boao Xia ◽

...

Keyword(s):

Histone Methylation ◽

Genetic Information ◽

Progenitor Cell ◽

Fibrous Tissue ◽

Cell Behavior ◽

Environmental Cues ◽

Chromatin Dynamics ◽

Phenotypic Changes ◽

Nano Scale ◽

Tissue Cells

AbstractMicroscale changes in tissue environment are translated to changes in cell behavior and phenotype, yet the mechanisms behind how these phenotypic changes occur are poorly understood. Here, we describe and model chromatin, which stores genetic information within the cell nucleus, as a dynamic nanomaterial whose configuration is modulated by chemo-mechanical cues in the microenvironment. Our findings indicate that physiologic chemo-mechanical cues can directly regulate chromatin architecture in progenitor cell populations. Via direct experimental observation and modeling that incorporates phase transitions and histone methylation kinetics, we demonstrate that soft environmental cues drive chromatin relocalization to the nuclear boundary and compaction. Conversely, dynamic stiffening attenuates these changes. Interestingly, in diseased human fibrous tissue cells, this link between mechanical inputs and chromatin nano-scale remodeling is abrogated. These data indicate that chromatin dynamics and plasticity may be hallmarks of disease progression and targets for therapeutic intervention.

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Intersections of lung progenitor cells, lung disease and lung cancer

European Respiratory Review ◽

10.1183/16000617.0054-2017 ◽

2017 ◽

Vol 26 (144) ◽

pp. 170054 ◽

Cited By ~ 7

Author(s):

Carla F. Kim

Keyword(s):

Lung Cancer ◽

Progenitor Cells ◽

Cell Biology ◽

Progenitor Cell ◽

Genetically Engineered ◽

Response To Therapy ◽

Culture Techniques ◽

Genetically Engineered Mouse Models ◽

Approaches To Study ◽

Lung Progenitor

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

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A Single Metabolite which Modulates Lipid Metabolism Alters Hematopoietic Stem/Progenitor Cell Behavior and Promotes Lymphoid Reconstitution

Stem Cell Reports ◽

10.1016/j.stemcr.2020.07.021 ◽

2020 ◽

Vol 15 (3) ◽

pp. 566-576

Author(s):

Sonja Giger ◽

Larisa V. Kovtonyuk ◽

Sebastian G. Utz ◽

Mergim Ramosaj ◽

Werner J. Kovacs ◽

...

Keyword(s):

Lipid Metabolism ◽

Progenitor Cell ◽

Cell Behavior ◽

Hematopoietic Stem

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Emerging roles for motor proteins in progenitor cell behavior and neuronal migration during brain development

Cytoskeleton ◽

10.1002/cm.21337 ◽

2016 ◽

Vol 73 (10) ◽

pp. Spc1-Spc1

Author(s):

Tiago J. Dantas ◽

Aurelie Carabalona ◽

Daniel Jun Kit Hu ◽

Richard B. Vallee

Keyword(s):

Brain Development ◽

Neuronal Migration ◽

Progenitor Cell ◽

Motor Proteins ◽

Cell Behavior

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S13-03 HOX transcription factor regulation of adult stem/progenitor cell behavior in response to injury

Mechanisms of Development ◽

10.1016/j.mod.2009.06.1026 ◽

2009 ◽

Vol 126 ◽

pp. S40-S41

Author(s):

Kimberly Mace

Keyword(s):

Transcription Factor ◽

Progenitor Cell ◽

Cell Behavior ◽

Transcription Factor Regulation

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Analyzing signaling activity and function in hematopoietic cells

Journal of Experimental Medicine ◽

10.1084/jem.20201546 ◽

2021 ◽

Vol 218 (7) ◽

Author(s):

Tobias Kull ◽

Timm Schroeder

Keyword(s):

Cell Signaling ◽

Signaling Pathways ◽

Progenitor Cell ◽

Cell Behavior ◽

Cell Fates ◽

Hematopoietic Stem ◽

Related Individual ◽

Health And Disease ◽

And Function ◽

Signaling Activity

Cells constantly sense their environment, allowing the adaption of cell behavior to changing needs. Fine-tuned responses to complex inputs are computed by signaling pathways, which are wired in complex connected networks. Their activity is highly context-dependent, dynamic, and heterogeneous even between closely related individual cells. Despite lots of progress, our understanding of the precise implementation, relevance, and possible manipulation of cellular signaling in health and disease therefore remains limited. Here, we discuss the requirements, potential, and limitations of the different current technologies for the analysis of hematopoietic stem and progenitor cell signaling and its effect on cell fates.

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