Research Paper|Volume 13, Issue 6|pp 8335—8354

HSCs transdifferentiate primarily to pneumonocytes in radiation-induced lung damage repair

Lei Li^1,^2,⁴, Suping Zhang^1,^2,^3,⁴, Chaorong Ge^1,², Li Ji^1,², Yaqi Lv^1,², Chen Zhao^1,^2,⁴, Li Xu^1,^2,⁴, Jingyi Zhang^1,², Chenglin Song^1,², Jianing Chen^1,², Wen Wei^1,^2,⁴, Yixuan Fang^1,^2,^3,⁴, Na Yuan^1,^2,^3,⁴, Jianrong Wang^1,^2,^3,⁴

¹Hematology Center of Cyrus Tang Medical Institute, Soochow University School of Medicine, Suzhou 215123, China
²National Clinical Research Center for Hematologic Diseases, Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
³State Key Laboratory of Radiation Medicine and Protection, Soochow University School of Medicine, Suzhou 215123, China
⁴Department of Hematopoietic Engineering, Susky Life SciTech (Suzhou) Co., Ltd., Suzhou 215124, China

* Equal contribution

Received: October 1, 2020Accepted: December 12, 2020Published: March 3, 2021

https://doi.org/10.18632/aging.202644

Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Accumulative radiation exposure leads to hematopoietic or tissue aging. Whether hematopoietic stem cells (HSCs) are involved in lung damage repair in response to radiation remains controversial. The aim of this study is to identify if HSC can transdifferentiate to pneumonocytes for radiation-induced damage repair. To this end, HSCs from male Rosa^mT/mG mice were isolated by fluorescence-activated cell sorting (FACS) and transplanted into lethally irradiated female CD45.1 mice. 4 months after transplantation, transplanted HSC was shown to repair the radiation-induced tissue damage, and donor-derived tdTomato (phycoerythrin, PE) red fluorescence cells and Ddx3y representing Y chromosome were detected exclusively in female recipient lung epithelial and endothelial cells. Co-localization of donor-derived cells and recipient lung tissue cells were observed by laser confocal microscopy and image flow cytometry. Furthermore, the results showed HSC transplantation replenished radiation-induced lung HSC depletion and the PE positive repaired lung epithelial cells were identified as donor HSC origin. The above data suggest that donor HSC may migrate to the injured lung of the recipient and some of them can be transdifferentiated to pneumonocytes to repair the injury caused by radiation.