Publications by authors named "Jiahn Choi"

5 Publications

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Author Correction: Intestinal crypts recover rapidly from focal damage with coordinated motion of stem cells that is impaired by aging.

Sci Rep 2019 Sep 30;9(1):13992. Epub 2019 Sep 30.

Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, 14853, USA.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-019-43805-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768855PMC
September 2019

Intestinal crypts recover rapidly from focal damage with coordinated motion of stem cells that is impaired by aging.

Sci Rep 2018 Jul 20;8(1):10989. Epub 2018 Jul 20.

Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, 14853, USA.

Despite the continuous renewal and turnover of the small intestinal epithelium, the intestinal crypt maintains a 'soccer ball-like', alternating pattern of stem and Paneth cells at the base of the crypt. To study the robustness of the alternating pattern, we used intravital two-photon microscopy in mice with fluorescently-labeled Lgr5+ intestinal stem cells and precisely perturbed the mosaic pattern with femtosecond laser ablation. Ablation of one to three cells initiated rapid motion of crypt cells that restored the alternation in the pattern within about two hours with only the rearrangement of pre-existing cells, without any cell division. Crypt cells then performed a coordinated dilation of the crypt lumen, which resulted in peristalsis-like motion that forced damaged cells out of the crypt. Crypt cell motion was reduced with inhibition of the ROCK pathway and attenuated with old age, and both resulted in incomplete pattern recovery. This suggests that in addition to proliferation and self-renewal, motility of stem cells is critical for maintaining homeostasis. Reduction of this newly-identified behavior of stem cells could contribute to disease and age-related changes.
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http://dx.doi.org/10.1038/s41598-018-29230-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054609PMC
July 2018

A Notch positive feedback in the intestinal stem cell niche is essential for stem cell self-renewal.

Mol Syst Biol 2017 04 28;13(4):927. Epub 2017 Apr 28.

School of Electrical and Computer Engineering, Cornell University, Ithaca, NY, USA

The intestinal epithelium is the fastest regenerative tissue in the body, fueled by fast-cycling stem cells. The number and identity of these dividing and migrating stem cells are maintained by a mosaic pattern at the base of the crypt. How the underlying regulatory scheme manages this dynamic stem cell niche is not entirely clear. We stimulated intestinal organoids with Notch ligands and inhibitors and discovered that intestinal stem cells employ a positive feedback mechanism via direct Notch binding to the second intron of the Notch1 gene. Inactivation of the positive feedback by CRISPR/Cas9 mutation of the binding sequence alters the mosaic stem cell niche pattern and hinders regeneration in organoids. Dynamical system analysis and agent-based multiscale stochastic modeling suggest that the positive feedback enhances the robustness of Notch-mediated niche patterning. This study highlights the importance of feedback mechanisms in spatiotemporal control of the stem cell niche.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408779PMC
http://dx.doi.org/10.15252/msb.20167324DOI Listing
April 2017

Simultaneous optical and electrical in vivo analysis of the enteric nervous system.

Nat Commun 2016 06 7;7:11800. Epub 2016 Jun 7.

School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA.

The enteric nervous system (ENS) is a major division of the nervous system and vital to the gastrointestinal (GI) tract and its communication with the rest of the body. Unlike the brain and spinal cord, relatively little is known about the ENS in part because of the inability to directly monitor its activity in live animals. Here, we integrate a transparent graphene sensor with a customized abdominal window for simultaneous optical and electrical recording of the ENS in vivo. The implanted device captures ENS responses to neurotransmitters, drugs and optogenetic manipulation in real time.
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http://dx.doi.org/10.1038/ncomms11800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899629PMC
June 2016

Comprehensive models of human primary and metastatic colorectal tumors in immunodeficient and immunocompetent mice by chemokine targeting.

Nat Biotechnol 2015 Jun 25;33(6):656-60. Epub 2015 May 25.

Department of Medicine, Weill Cornell Medical College, New York, New York, USA.

Current orthotopic xenograft models of human colorectal cancer (CRC) require surgery and do not robustly form metastases in the liver, the most common site clinically. CCR9 traffics lymphocytes to intestine and colorectum. We engineered use of the chemokine receptor CCR9 in CRC cell lines and patient-derived cells to create primary gastrointestinal (GI) tumors in immunodeficient mice by tail-vein injection rather than surgery. The tumors metastasize inducibly and robustly to the liver. Metastases have higher DKK4 and NOTCH signaling levels and are more chemoresistant than paired subcutaneous xenografts. Using this approach, we generated 17 chemokine-targeted mouse models (CTMMs) that recapitulate the majority of common human somatic CRC mutations. We also show that primary tumors can be modeled in immunocompetent mice by microinjecting CCR9-expressing cancer cell lines into early-stage mouse blastocysts, which induces central immune tolerance. We expect that CTMMs will facilitate investigation of the biology of CRC metastasis and drug screening.
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http://dx.doi.org/10.1038/nbt.3239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532544PMC
June 2015