Genetic lineage tracing reveals stellate cells as contributors to myofibroblasts in pancreas and islet fibrosis

Jinbang Wang; Tingting Li; Yunting Zhou; Xiaohang Wang; Vladmir Carvalho; Chengming Ni; Wei Li; Qianqian Wang; Yang Chen; Zhanjia Shang; Shanhu Qiu; Zilin Sun

doi:10.1016/j.isci.2023.106988

Genetic lineage tracing reveals stellate cells as contributors to myofibroblasts in pancreas and islet fibrosis

iScience. 2023 May 26;26(6):106988. doi: 10.1016/j.isci.2023.106988. eCollection 2023 Jun 16.

Authors

Affiliations

¹ Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China.
² Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
³ Department of Endocrinology, Suzhou Hospital of Anhui Medical University, Suzhou, China.
⁴ Department of General Practice, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China.

Abstract

Pancreatic stellate cells (PSCs) are suggested to play an important role in the development of pancreas and islet fibrosis. However, the precise contributions and solid in vivo evidence of PSCs to the fibrogenesis remain to be elucidated. Here, we developed a novel fate-tracing strategy for PSCs by vitamin A administration in Lrat-cre; Rosa26-tdTomato transgenic mouse. The results showed that stellate cells give rise to 65.7% of myofibroblasts in cerulein-induced pancreatic exocrine fibrosis. In addition, stellate cells in islets increase and contribute partly to myofibroblasts pool in streptozocin-induced acute or chronic islet injury and fibrosis. Furthermore, we substantiated the functional contribution of PSCs to fibrogenesis of pancreatic exocrine and islet in PSCs ablated mice. We also found stellate cells' genetic ablation can improve pancreatic exocrine but not islet fibrosis. Together, our data indicates that stellate cells are vital/partial contributors to myofibroblasts in pancreatic exocrine/islet fibrosis.

Keywords: Cell biology; Endocrinology.