Article
Version 1
Preserved in Portico This version is not peer-reviewed
LGR5+ Intestinal Stem Cells Display Sex Dependent Radiosensitivity
Version 1
: Received: 14 November 2023 / Approved: 15 November 2023 / Online: 15 November 2023 (13:57:04 CET)
A peer-reviewed article of this Preprint also exists.
Zitter, R.C.; Chugh, R.M.; Bhanja, P.; Kimler, B.F.; Saha, S. LGR5+ Intestinal Stem Cells Display Sex-Dependent Radiosensitivity. Cells 2024, 13, 46. Zitter, R.C.; Chugh, R.M.; Bhanja, P.; Kimler, B.F.; Saha, S. LGR5+ Intestinal Stem Cells Display Sex-Dependent Radiosensitivity. Cells 2024, 13, 46.
Abstract
Radiosensitivity, the susceptibility of cells to ionizing radiation, plays a critical role in understanding the effects of radiation therapy and exposure on tissue health and regeneration. Identifying characteristics that predict how a patient may respond to radiotherapy enables clinicians to maximize the therapeutic window. Limited clinical data suggested a difference in male and female radiotherapy outcomes. Radiotherapy for gastrointestinal malignancy is still a challenge due to intestinal sensitivity to radiation toxicity. In this manuscript we demonstrated sex specific differences in intestinal epithelial radiosensitivity. In mice model of abdominal irradiation, we observed significant increase in oxidative stress and injury in male compared to female. Lgr5+ve intestinal stem cells from male mice showed higher sensitivity to radiation induced toxicity. However, sex specific differences in intestinal radiosensitivity are not dependent on sex hormone as we demonstrated similar sex specific radiosensitivity differences in pediatric mice. In ex-vivo study we found that human patient derived intestinal organoid (PID) derived from male showed higher sensitivity to irradiation compared to female as evident from loss of budding crypt, organoid size, and membrane integrity. Transcriptomic analysis of human Lgr5+ intestinal stem cells suggested radiation induced upregulation of mitochondrial oxidative metabolism in male compared to female possible mechanism for radiosensitivity differences.
Keywords
LGR5+; radiosensitivity; oxidative-stress; ISCs
Subject
Biology and Life Sciences, Cell and Developmental Biology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comments (0)
We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.
Leave a public commentSend a private comment to the author(s)
* All users must log in before leaving a comment