scholarly journals Defining Epidermal Basal Cell States During Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics

2019 ◽  
Author(s):  
Daniel Haensel ◽  
Suoqin Jin ◽  
Rachel Cinco ◽  
Peng Sun ◽  
Quy H. Nguyen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Single Cell ◽  
Basal Cell

scholarly journals Defining epidermal basal cell states during skin homeostasis and wound healing using single-cell transcriptomics

2019 ◽  
Author(s):  
Daniel Haensel ◽  
Suoqin Jin ◽  
Rachel Cinco ◽  
Peng Sun ◽  
Quy Nguyen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Single Cell ◽  
Basal Cell ◽  
Early Response ◽  
Fluorescence Lifetime Imaging ◽  
Basal Cells ◽  
Cell Dynamics ◽  
Cell Compartments ◽  
Cutaneous Tissue ◽  
Response State

SUMMARYOur knowledge of transcriptional heterogeneities in epithelial stem/progenitor cell compartments is limited. Epidermal basal cells sustain cutaneous tissue maintenance and drive wound healing. Previous studies have probed basal cell heterogeneity in stem/progenitor potential, but a non-biased dissection of basal cell dynamics during differentiation is lacking. Using single-cell RNA-sequencing coupled with RNAScope and fluorescence lifetime imaging, we identify three non-proliferative and one proliferative basal cell transcriptional states in homeostatic skin that differ in metabolic preference and become spatially partitioned during wound re-epithelialization. Pseudotemporal trajectory and RNA velocity analyses produce a quasi-linear differentiation hierarchy where basal cells progress from Col17a1high/Trp63high state to early response state, proliferate at the juncture of these two states, or become growth arrested before differentiating into spinous cells. Wound healing induces plasticity manifested by dynamic basal-spinous interconversions at multiple basal states. Our study provides a systematic view of epidermal cellular dynamics supporting a revised “hierarchical-lineage” model of homeostasis.

scholarly journals Defining Epidermal Basal Cell States during Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics

Cell Reports ◽  
2020 ◽  
Vol 30 (11) ◽  
pp. 3932-3947.e6 ◽  
Author(s):  
Daniel Haensel ◽  
Suoqin Jin ◽  
Peng Sun ◽  
Rachel Cinco ◽  
Morgan Dragan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Single Cell ◽  
Basal Cell

scholarly journals Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures

2020 ◽  
Author(s):  
Ameen A. Salahudeen ◽  
Shannon S. Choi ◽  
Arjun Rustagi ◽  
Junjie Zhu ◽  
Sean M. de la O ◽  
...  
Keyword(s):  
Lung Disease ◽  
Single Cell ◽  
Basal Cell ◽  
Human Lung ◽  
Basal Cells ◽  
Ciliated Cells ◽  
Club Cells ◽  
Distal Lung

ABSTRACTThe distal lung contains terminal bronchioles and alveoli that facilitate gas exchange and is affected by disorders including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. Investigations of these localized pathologies have been hindered by a lack of 3D in vitro human distal lung culture systems. Further, human distal lung stem cell identification has been impaired by quiescence, anatomic divergence from mouse and lack of lineage tracing and clonogenic culture. Here, we developed robust feeder-free, chemically-defined culture of distal human lung progenitors as organoids derived clonally from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids exhibited AT1 transdifferentiation potential, while basal cell organoids progressively developed lumens lined by differentiated club and ciliated cells. Organoids consisting solely of club cells were not observed. Upon single cell RNA-sequencing (scRNA-seq), alveolar organoids were composed of proliferative AT2 cells; however, basal organoid KRT5+ cells contained a distinct ITGA6+ITGB4+ mitotic population whose proliferation segregated to a TNFRSF12Ahi subfraction. Clonogenic organoid growth was markedly enriched within the TNFRSF12Ahi subset of FACS-purified ITGA6+ITGB4+ basal cells from human lung or derivative organoids. In vivo, TNFRSF12A+ cells comprised ~10% of KRT5+ basal cells and resided in clusters within terminal bronchioles. To model COVID-19 distal lung disease, we everted the polarity of basal and alveolar organoids to rapidly relocate differentiated club and ciliated cells from the organoid lumen to the exterior surface, thus displaying the SARS-CoV-2 receptor ACE2 on the outwardly-facing apical aspect. Accordingly, basal and AT2 “apical-out” organoids were infected by SARS-CoV-2, identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung alveolar and basal stem cells, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and exemplifies progenitor identification within a slowly proliferating human tissue. Further, our studies establish a facile in vitro organoid model for human distal lung infectious diseases including COVID-19-associated pneumonia.

scholarly journals Basal stem cell fate specification is mediated by SMAD signaling in the developing human lung

2018 ◽  
Author(s):  
Alyssa J. Miller ◽  
Qianhui Yu ◽  
Michael Czerwinski ◽  
Yu-Hwai Tsai ◽  
Renee F. Conway ◽  
...  
Keyword(s):  
Single Cell ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Basal Cell ◽  
Human Lung ◽  
Branching Morphogenesis ◽  
Basal Cells ◽  
Smad Signaling ◽  
Cell Fate Decisions ◽  
Cell Transition

AbstractBasal stem cells (basal cells), located in the bronchi and trachea of the human lung epithelium, play a critical role in normal airway homeostasis and repair, and have been implicated in the development of diseases such as cancer1-4. Additionally, basal-like cells contribute to alveolar regeneration and fibrosis following severe injury5-8. However, the developmental origin of basal cells in humans is unclear. Previous work has shown that specialized progenitor cells exist at the tips of epithelial tubes during lung branching morphogenesis, and in mice, give rise to all alveolar and airway lineages9,10. These ‘bud tip progenitor cells’ have also been described in the developing human lung11-13, but the mechanisms controlling bud tip differentiation into specific cell lineages, including basal cells, are unknown. Here, we interrogated the bud tip-to-basal cell transition using human tissue specimens, bud tip progenitor organoid cultures11, and single-cell transcriptomics. We used single-cell mRNA sequencing (scRNAseq) of developing human lung specimens from 15-21 weeks gestation to identify molecular signatures and cell states in the developing human airway epithelium. We then inferred differentiation trajectories during bud tip-to-airway differentiation, which revealed a previously undescribed transitional cell state (‘hub progenitors’) and implicated SMAD signaling as a regulator of the bud tip-to-basal cell transition. We used bud tip progenitor organoids to show that TGFT1 and BMP4 mediated SMAD signaling robustly induced the transition into functional basal-like cells, and these in vitro-derived basal cells exhibited clonal expansion, self-renewal and multilineage differentiation. This work provides a framework for deducing and validating key regulators of cell fate decisions using single cell transcriptomics and human organoid models. Further, the identification of SMAD signaling as a critical regulator of newly born basal cells in the lung may have implications for regenerative medicine, basal cell development in other organs, and understanding basal cell misregulation in disease.

Conjunctivalization of Meibomian Glands following Cryosurgery for Basal Cell Carcinoma of the Eyelid

1994 ◽  
Vol 4 (1) ◽  
pp. 59-61 ◽  
Author(s):  
B. Daicker ◽  
S. Büchner ◽  
M. Kraus
Keyword(s):  
Wound Healing ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Conjunctival Epithelium ◽  
Tarsal Plate ◽  
Meibomian Glands ◽  
Peculiar Change ◽  
Supporting Structures

Cryosurgery on the eyelids destroys the cellular elements in the frozen region, but preserves the collagenous supporting structures. Cells from the neighborhood colonize this framework during wound healing. The Authors describe a peculiar change in the Meibomian glands, which obviously developed by this mechanism in a lid treated by cryotherapy for a basal cell carcinoma. The collagenous lodges of the Meibomian glands, denuded of their sebaceous cells by the therapy, were epithelialized by ingrown conjunctival epithelium. This situation seems to promote the spread of and maintain acute and chronic exogenous inflammation in the tarsal plate.

scholarly journals Annexins: players of single cell wound healing and regeneration

2019 ◽  
Vol 12 (1) ◽  
pp. 162-165 ◽  
Author(s):  
Swantje Christin Häger ◽  
Jesper Nylandsted
Keyword(s):  
Wound Healing ◽  
Single Cell

scholarly journals Study of Wound Healing Dynamics by Single Pseudo-Particle Tracking in Phase Contrast Images Acquired in Time-Lapse

Entropy ◽  
2021 ◽  
Vol 23 (3) ◽  
pp. 284
Author(s):  
Riccardo Scheda ◽  
Silvia Vitali ◽  
Enrico Giampieri ◽  
Gianni Pagnini ◽  
Isabella Zironi
Keyword(s):  
Wound Healing ◽  
Single Cell ◽  
Particle Tracking ◽  
Single Particle ◽  
Phase Contrast ◽  
Time Lapse ◽  
Single Particle Tracking ◽  
Stochastic Motion ◽  
Wound Edge ◽  
Scratch Assay

Cellular contacts modify the way cells migrate in a cohesive group with respect to a free single cell. The resulting motion is persistent and correlated, with cells’ velocities self-aligning in time. The presence of a dense agglomerate of cells makes the application of single particle tracking techniques to define cells dynamics difficult, especially in the case of phase contrast images. Here, we propose an original pipeline for the analysis of phase contrast images of the wound healing scratch assay acquired in time-lapse, with the aim of extracting single particle trajectories describing the dynamics of the wound closure. In such an approach, the membrane of the cells at the border of the wound is taken as a unicum, i.e., the wound edge, and the dynamics is described by the stochastic motion of an ensemble of points on such a membrane, i.e., pseudo-particles. For each single frame, the pipeline of analysis includes: first, a texture classification for separating the background from the cells and for identifying the wound edge; second, the computation of the coordinates of the ensemble of pseudo-particles, chosen to be uniformly distributed along the length of the wound edge. We show the results of this method applied to a glioma cell line (T98G) performing a wound healing scratch assay without external stimuli. We discuss the efficiency of the method to assess cell motility and possible applications to other experimental layouts, such as single cell motion. The pipeline is developed in the Python language and is available upon request.

Morpheaform Basal Cell Carcinomas With Areas of Predominantly Single-Cell Pattern of Infiltration

2016 ◽  
Vol 38 (10) ◽  
pp. 744-750 ◽  
Author(s):  
Ellen East ◽  
Douglas R. Fullen ◽  
David Arps ◽  
Rajiv M. Patel ◽  
Nallasivam Palanisamy ◽  
...  
Keyword(s):  
Single Cell ◽  
Basal Cell ◽  
Cell Pattern ◽  
Basal Cell Carcinomas

scholarly journals Identification of a basal stem cell subpopulation in the prostate via functional, lineage tracing and single-cell RNA-seq analyses

2019 ◽  
Author(s):  
Xue Wang ◽  
Haibo Xu ◽  
Chaping Cheng ◽  
Zhongzhong Ji ◽  
Huifang Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Epithelial Cells ◽  
Single Cell ◽  
Basal Cell ◽  
Lineage Tracing ◽  
Cell Subpopulation ◽  
Basal Cells ◽  
Mesenchymal Transition ◽  
Genetic Ablation

AbstractThe basal cell compartment in many epithelial tissues such as the prostate, bladder, and mammary gland are generally believed to serve as an important pool of stem cells. However, basal cells are heterogenous and the stem cell subpopulation within basal cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb is exclusively expressed in a prostate basal cell subpopulation based on both immunocytochemical and cell lineage tracing analysis. The Zeb1+prostate epithelial cells are multipotent prostate basal stem cells (PBSCs) that can self-renew and generate functional prostatic glandular structures with all three epithelial cell types at the single-cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal cell development. Utilizing unbiased single cell transcriptomic analysis of over 9000 mouse prostate basal cells, we find that Zeb1+basal cell subset shares gene expression signatures with both epithelial and mesenchymal cells and stands out uniquely among all the basal cell clusters. Moreover, Zeb1+epithelial cells can be detected in mouse and clinical samples of prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis.

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