Single-cell analysis of circadian dynamics in tissue explants
Open accessAbstract
Tracking molecular dynamics in single cells in vivo is instrumental to understanding how cells act and interact in tissues. Current tissue imaging approaches focus on short-term observation and typically nonendogenous or implanted samples. Here we develop an experimental and computational setup that allows for single-cell tracking of a transcriptional reporter over a period of >1 wk in the context of an intact tissue. We focus on the peripheral circadian clock as a model system and measure the circadian signaling of hundreds of cells from two tissues. The circadian clock is an autonomous oscillator whose behavior is well described in isolated cells, but in situ analysis of circadian signaling in single cells of peripheral tissues is as-yet uncharacterized. Our approach allowed us to investigate the oscillatory properties of individual clocks, determine how these properties are maintained among different cells, and assess how they compare to the population rhythm. These experiments, using a wide-field microscope, a previously generated reporter mouse, and custom software to track cells over days, suggest how many signaling pathways might be quantitatively characterized in explant models.
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Distance metrics become unstable in high-dimensional space, which obstructs clustering there.
“Clustering in high-dimensional space is obstructed by the instability of distance metrics in high dimension103 (which is a facet of the ‘curse of dimensionality’).”
From Revealing the vectors of cellular identity with single-cell genomics (2016) · cites this paper as [103]
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References 35 · Cited by 22
- Authors
- Lande-Diner, L., Stewart-Ornstein, J., Weitz, C. J., & Lahav, G.
- Affiliations
- Department of Neurobiology, Harvard Medical School, Boston, MA 02115
- Harvard University (US)
- Corresponding author
- Weitz, Charles J.
- Lahav, Galit
- Venue
- Molecular Biology of the Cell
- Published
- 2015-11-05
- Volume
- 26
- Issue
- 22
- Pages
- 3940-3945
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC4710227
- OpenAlex
- W2104602564
- Cited by
- 22
- References
- 35
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 1 · 2021: 2 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 4
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- Molecular Biology of the Cell (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institute of General Medical Sciences (R01GM083303, GM083303)
- National Institute of Neurological Disorders and Stroke (#NS072030, P30NS072030)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- circadian clock, peripheral circadian clock, single-cell tracking, tissue explants, transcriptional reporter, in vivo imaging, wide-field microscopy
- MeSH terms
- Animals, Bone and Bones, Circadian Rhythm, Mice, Transgenic, Nuclear Proteins, Software, Tendons, Transcription Factors, Models, Animal, Mice, Period Circadian Proteins, Circadian Clocks, Single-Cell Analysis, Plant Cells
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