title: Notch signalling regulates asymmetric division and inter-conversion between lgr5 and bmi1 expressing intestinal stem cells.
abstract: Rapidly cycling LGR5+ intestinal stem cells (ISCs) located at the base of crypts are the primary driver of regeneration. Additionally, BMI1 expression is correlated with a slow cycling pool of ISCs located at +4 position. While previous reports have shown interconversion between these two populations following tissue injury, we provide evidence that NOTCH signaling regulates the balance between these two populations and promotes asymmetric division as a mechanism for interconversion in the mouse intestine. In both in vitro and in vivo models, NOTCH suppression reduces the ratio of BMI1+/LGR5+ ISCs while NOTCH stimulation increases this ratio. Furthermore, NOTCH signaling can activate asymmetric division after intestinal inflammation. Overall, these data provide insights into ISC plasticity, demonstrating a direct interconversion mechanism between slow- and fast-cycling ISCs.
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, 14853, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Srinivasan
authors.affiliation: Departments of Medicine, Surgery and Pathology, Weill Cornell Medical College, New York City, New York, 10021, USA.
authors.forename: Elaine Bich
authors.initials: EB
authors.lastname: Than
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, 14853, USA.|School of Electrical and Computer Engineering, Cornell University, Ithaca, New York, 14853, USA.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Bu
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York, 14853, USA.
authors.forename: Kuei-Ling
authors.initials: KL
authors.lastname: Tung
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, 14853, USA.
authors.forename: Kai-Yuan
authors.initials: KY
authors.lastname: Chen
authors.affiliation: Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, 10461 USA.
authors.forename: Leonard
authors.initials: L
authors.lastname: Augenlicht
authors.affiliation: Departments of Medicine, Surgery and Pathology, Weill Cornell Medical College, New York City, New York, 10021, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Lipkin
authors.affiliation: Department of Biomedical Engineering, Cornell University, Ithaca, New York, 14853, USA.|School of Electrical and Computer Engineering, Cornell University, Ithaca, New York, 14853, USA.|Department of Biomedical Engineering, Duke University, Durham, North Carolina, 27708 USA.
authors.forename: Xiling
authors.initials: X
authors.lastname: Shen
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D002455:Cell Division; D000066670:Cell Plasticity; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D007422:Intestines / Q000166:cytology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D012038:Regeneration; D015398:Signal Transduction
chemical_list: C489421:Bmi1 protein, mouse; C493597:Lgr5 protein, mouse; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D051880:Receptors, Notch; D063150:Polycomb Repressive Complex 1