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Article ; Online: Advances in Mapping Tumor Progression from Precancer Atlases.

Chen, Zhengyi / Lau, Ken S

Cancer prevention research (Philadelphia, Pa.)

2023 Volume 16, Issue 8, Page(s) 439–447

Abstract: Tissue profiling technologies present opportunities for understanding transition from precancerous lesions to malignancy, which may impact risk stratification, prevention, and even cancer treatment. A human precancer atlas building effort is ongoing to ... ...

Abstract	Tissue profiling technologies present opportunities for understanding transition from precancerous lesions to malignancy, which may impact risk stratification, prevention, and even cancer treatment. A human precancer atlas building effort is ongoing to tackle the significant challenge of decoding the heterogeneity among cells, specimens, and patients. Here, we discuss the findings resulting from atlases built across precancer types, including those found in colon, breast, lung, stomach, cervix, and skin, using bulk, single-cell, and spatial profiling strategies. We highlight two main themes that emerge across precancer types: the ordering of molecular events that occur during tumor progression and the fluctuation of microenvironmental response during precancer progression. We further highlight the key challenges of data integration across large cohorts of patients, and the need for computational tools to reliably annotate and quality control high-volume, high-dimensional data.
MeSH term(s)	Female ; Humans ; Precancerous Conditions/pathology ; Cervix Uteri/pathology ; Breast/pathology ; Skin/pathology
Language	English
Publishing date	2023-05-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2434717-6
ISSN	1940-6215 ; 1940-6207
ISSN (online)	1940-6215
ISSN	1940-6207
DOI	10.1158/1940-6207.CAPR-22-0473
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Article ; Online: Dissociation and inDrops microfluidic encapsulation of human gut tissues for single-cell atlasing studies.

Simmons, Alan J / Lau, Ken S

STAR protocols

2022 Volume 3, Issue 3, Page(s) 101570

Abstract: In droplet-based single-cell RNA-sequencing (scRNA-seq) experiments, cells, along with some of their surrounding buffer and ambient material, are encapsulated into droplets for mRNA capture and barcoding. This protocol details the steps for human gut ... ...

Abstract	In droplet-based single-cell RNA-sequencing (scRNA-seq) experiments, cells, along with some of their surrounding buffer and ambient material, are encapsulated into droplets for mRNA capture and barcoding. This protocol details the steps for human gut tissue dissociation using cold active protease, and subsequent isolation of single epithelial cells, with enrichment of viability through washes. Next, the steps for encapsulation on the inDrops scRNA-seq platform are described. This procedure has been demonstrated to be applicable to polyps, cancers, and inflamed tissues. For complete details on the use and execution of this protocol, please refer to Chen et al. (2021).
MeSH term(s)	Humans ; Microfluidics ; Neoplasms ; RNA, Messenger ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2022-07-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2022.101570
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Intestinal tuft cells assemble a cytoskeletal superstructure composed of co-aligned actin bundles and microtubules.

Silverman, Jennifer B / Krystofiak, Evan E / Caplan, Leah R / Lau, Ken S / Tyska, Matthew J

bioRxiv : the preprint server for biology

2024

Abstract: Background & aims: All tissues consist of a distinct set of cell types, which collectively support organ function and homeostasis. Tuft cells are a rare epithelial cell type found in diverse epithelia, where they play important roles in sensing antigens ...

Abstract	Background & aims: All tissues consist of a distinct set of cell types, which collectively support organ function and homeostasis. Tuft cells are a rare epithelial cell type found in diverse epithelia, where they play important roles in sensing antigens and stimulating downstream immune responses. Exhibiting a unique polarized morphology, tuft cells are defined by an array of giant actin filament bundles that support ∼2 μm of apical membrane protrusion and extend over 7 μm towards the cell's perinuclear region. Despite their established roles in maintaining intestinal epithelial homeostasis, tuft cells remain understudied due to their rarity (e.g. ∼ 1% in the small intestinal epithelium). Details regarding the ultrastructural organization of the tuft cell cytoskeleton, the molecular components involved in building the array of giant actin bundles, and how these cytoskeletal structures support tuft cell biology remain unclear. Methods: To begin to answer these questions, we used advanced light and electron microscopy to perform quantitative morphometry of the small intestinal tuft cell cytoskeleton. Results: We found that tuft cell core bundles consist of actin filaments that are crosslinked in a parallel "barbed-end out" configuration. These polarized structures are also supported by a unique group of tuft cell enriched actin-binding proteins that are differentially localized along the giant core bundles. Furthermore, we found that tuft cell actin bundles are co-aligned with a highly ordered network of microtubules. Conclusions: Tuft cells assemble a cytoskeletal superstructure that is well positioned to serve as a track for subcellular transport along the apical-basolateral axis and in turn, support the dynamic sensing functions that are critical for intestinal epithelial homeostasis. Synopsis: This research leveraged advanced light and electron microscopy to perform quantitative morphometry of the intestinal tuft cell cytoskeleton. Three-dimensional reconstructions of segmented image data revealed a co-aligned actin-microtubule superstructure that may play a fundamental role in tuft cell function.
Language	English
Publishing date	2024-03-19
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.19.585757
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Intestinal Tuft Cells: Morphology, Function, and Implications for Human Health.

Silverman, Jennifer B / Vega, Paige N / Tyska, Matthew J / Lau, Ken S

Annual review of physiology

2023 Volume 86, Page(s) 479–504

Abstract: Tuft cells are a rare and morphologically distinct chemosensory cell type found throughout many organs, including the gastrointestinal tract. These cells were identified by their unique morphologies distinguished by large apical protrusions. ... ...

Abstract	Tuft cells are a rare and morphologically distinct chemosensory cell type found throughout many organs, including the gastrointestinal tract. These cells were identified by their unique morphologies distinguished by large apical protrusions. Ultrastructural data have begun to describe the molecular underpinnings of their cytoskeletal features, and tuft cell-enriched cytoskeletal proteins have been identified, although the connection of tuft cell morphology to tuft cell functionality has not yet been established. Furthermore, tuft cells display variations in function and identity between and within tissues, leading to the delineation of distinct tuft cell populations. As a chemosensory cell type, they display receptors that are responsive to ligands specific for their environment. While many studies have demonstrated the tuft cell response to protists and helminths in the intestine, recent research has highlighted other roles of tuft cells as well as implicated tuft cells in other disease processes including inflammation, cancer, and viral infections. Here, we review the literature on the cytoskeletal structure of tuft cells. Additionally, we focus on new research discussing tuft cell lineage, ligand-receptor interactions, tuft cell tropism, and the role of tuft cells in intestinal disease. Finally, we discuss the implication of tuft cell-targeted therapies in human health and how the morphology of tuft cells may contribute to their functionality.
MeSH term(s)	Humans ; Intestinal Mucosa/metabolism ; Tuft Cells ; Intestines ; Gastrointestinal Tract ; Cell Lineage
Language	English
Publishing date	2023-10-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	207933-1
ISSN	1545-1585 ; 0066-4278
ISSN (online)	1545-1585
ISSN	0066-4278
DOI	10.1146/annurev-physiol-042022-030310
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Article ; Online: A Quantitative Framework for Evaluating Single-Cell Data Structure Preservation by Dimensionality Reduction Techniques.

Heiser, Cody N / Lau, Ken S

Cell reports

2020 Volume 31, Issue 5, Page(s) 107576

Abstract: High-dimensional data, such as those generated by single-cell RNA sequencing (scRNA-seq), present challenges in interpretation and visualization. Numerical and computational methods for dimensionality reduction allow for low-dimensional representation of ...

Abstract	High-dimensional data, such as those generated by single-cell RNA sequencing (scRNA-seq), present challenges in interpretation and visualization. Numerical and computational methods for dimensionality reduction allow for low-dimensional representation of genome-scale expression data for downstream clustering, trajectory reconstruction, and biological interpretation. However, a comprehensive and quantitative evaluation of the performance of these techniques has not been established. We present an unbiased framework that defines metrics of global and local structure preservation in dimensionality reduction transformations. Using discrete and continuous real-world and synthetic scRNA-seq datasets, we show how input cell distribution and method parameters are largely determinant of global, local, and organizational data structure preservation by 11 common dimensionality reduction methods.
MeSH term(s)	Algorithms ; Cluster Analysis ; Gene Expression Profiling ; Humans ; RNA, Small Cytoplasmic/genetics ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; Transcriptome/genetics ; Exome Sequencing/methods
Chemical Substances	RNA, Small Cytoplasmic
Language	English
Publishing date	2020-05-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2020.107576
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Deciphering the cancer microenvironment from bulk data with EcoTyper.

Rolong, Andrea / Chen, Bob / Lau, Ken S

Cell

2021 Volume 184, Issue 21, Page(s) 5306–5308

Abstract: In this issue of Cell, Luca, Steen et al. develop the EcoTyper software to deconvolve tumor-microenvironment interactions from high volume bulk transcriptomics data. They demonstrate its effectiveness in improving predictions for tumor progression and ... ...

Abstract	In this issue of Cell, Luca, Steen et al. develop the EcoTyper software to deconvolve tumor-microenvironment interactions from high volume bulk transcriptomics data. They demonstrate its effectiveness in improving predictions for tumor progression and patient prognosis for a variety of tumor types from multiple data sources.
MeSH term(s)	Humans ; Neoplasms/genetics ; Software ; Transcriptome ; Tumor Microenvironment
Language	English
Publishing date	2021-11-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.09.028
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 58: Show issues

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Article ; Online: Protecting the Right Ventricle Network (PRORVNet): Time to Defend the "Forgotten Ventricle"?

Zochios, Vasileios / Lau, Gary / Conway, Hannah / Parhar, Ken Kuljit S

Journal of cardiothoracic and vascular anesthesia

2021 Volume 35, Issue 6, Page(s) 1565–1567

MeSH term(s)	Heart Ventricles/diagnostic imaging ; Humans
Language	English
Publishing date	2021-01-08
Publishing country	United States
Document type	Editorial
ZDB-ID	1067317-9
ISSN	1532-8422 ; 1053-0770
ISSN (online)	1532-8422
ISSN	1053-0770
DOI	10.1053/j.jvca.2021.01.002
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Zs.A 2203: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 31: Show issues

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Article: Use of mobile app to enhance functional outcomes and adherence of home-based rehabilitation program for elderly with hip fracture: A randomized controlled trial.

Cheng, Kui Ching / Lau, Kin Ming Ken / Cheng, Andy S K / Lau, Tin Sing Keith / Lau, Fuk On Titanic / Lau, Mun Cheung Herman / Law, Sheung Wai

Hong Kong physiotherapy journal : official publication of the Hong Kong Physiotherapy Association Limited = Wu li chih liao

2022 Volume 42, Issue 2, Page(s) 99–110

Abstract: Background: Mobile app has been used to improve exercise adherence and outcomes in populations with different health conditions. However, the effectiveness of mobile app in delivering home-based rehabilitation program to elderly patients with hip ... ...

Abstract	Background: Mobile app has been used to improve exercise adherence and outcomes in populations with different health conditions. However, the effectiveness of mobile app in delivering home-based rehabilitation program to elderly patients with hip fracture is unclear. Objective: The aim of this study was to test the effectiveness of mobile app in delivering home-based rehabilitation program for improving functional outcomes and reducing caregiver stress with enhancing adherence among the elderly patients with hip fracture. Methods: A randomized controlled trial with an intervention period of two months was performed. Eligible participants were randomized into either experimental group with home-based rehabilitation program using a mobile app or control group with home-based rehabilitation program using an exercise pamphlet. Primary outcomes were Modified Functional Ambulatory Category (MFAC), Elderly Mobility Scale (EMS) and Lower Extremity Functional Scale (LEFS). Secondary outcomes were exercise adherence and Modified Caregiver Strain Index (M-CSI). The outcomes were collected at pre-discharge training session, one month and two months after hospital discharge. Results: A total of 50 participants were enrolled, with 19 participants in the experimental group and 20 participants in the control group. Eleven participants had withdrawn from the study. The experimental group showed higher exercise adherence than the control group in first month ( Conclusion: Use of the mobile app improved exercise adherence, yet it did not improve physical performance, self-efficacy and reduce caregiver stress when compared to a standard home rehabilitation program for elderly patients with hip fracture. Further studies to investigate the benefits of mobile apps are required. (ClinicalTrials.gov ID: NCT04053348.).
Language	English
Publishing date	2022-06-15
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2202255-7
ISSN	1876-441X ; 1013-7025
ISSN (online)	1876-441X
ISSN	1013-7025
DOI	10.1142/S101370252250010X
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Article: Deciphering the cancer microenvironment from bulk data with EcoTyper

Rolong, Andrea / Chen, Bob / Lau, Ken S.

Cell. 2021 Oct. 14, v. 184, no. 21

2021

Abstract	In this issue of Cell, Luca, Steen et al. develop the EcoTyper software to deconvolve tumor-microenvironment interactions from high volume bulk transcriptomics data. They demonstrate its effectiveness in improving predictions for tumor progression and patient prognosis for a variety of tumor types from multiple data sources.
Keywords	computer software ; neoplasm progression ; neoplasms ; patients ; prognosis ; transcriptomics
Language	English
Dates of publication	2021-1014
Size	p. 5306-5308.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.09.028
Database	NAL-Catalogue (AGRICOLA)

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Z 93: Show issues

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Article ; Online: Not All Insults Are Created Equal for Awakening Dormant Stem Cell Abilities.

Vega, Paige N / Lau, Ken S / Goldenring, James R

Cellular and molecular gastroenterology and hepatology

2019 Volume 7, Issue 3, Page(s) 619–621

MeSH term(s)	Cell Count ; Cell Plasticity ; Paneth Cells ; Stem Cells
Language	English
Publishing date	2019-01-07
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2819778-1
ISSN	2352-345X ; 2352-345X
ISSN (online)	2352-345X
ISSN	2352-345X
DOI	10.1016/j.jcmgh.2018.12.003
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