KLF2 Orchestrates Pathological Progression of Infantile Hemangioma through Hemangioma Stem Cell Fate Decisions

Qiming Chen; Hao Rong; Ling Zhang; Yanan Wang; Qian Bian; Jiawei Zheng

doi:10.1016/j.jid.2024.01.029

KLF2 Orchestrates Pathological Progression of Infantile Hemangioma through Hemangioma Stem Cell Fate Decisions

J Invest Dermatol. 2024 Feb 19:S0022-202X(24)00113-1. doi: 10.1016/j.jid.2024.01.029. Online ahead of print.

Authors

Qiming Chen¹, Hao Rong², Ling Zhang¹, Yanan Wang¹, Qian Bian³, Jiawei Zheng⁴

Affiliations

¹ Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China.
² Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China.
³ Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China. Electronic address: qianbian@shsmu.edu.cn.
⁴ Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, 200011, China. Electronic address: davidzhengjw@hotmail.com.

PMID: 38382868
DOI: 10.1016/j.jid.2024.01.029

Abstract

Infantile hemangioma (IH) is the most prevalent vascular tumor during infancy, characterized by a rapid proliferation phase of disorganized blood vessels and spontaneous involution. IH possibily arises from a special type of multipotent stem cells called hemangioma stem cells (HemSCs), which could differentiate into endothelial cells, pericytes, and adipocytes. However, the underlying mechanisms that regulate the cell fate determination of HemSCs remain elusive. Here, we unveil KLF2 as a candidate transcription factor involved in the control of HemSCs differentiation. KLF2 exhibits high expression in endothelial cells in proliferating IH but diminishes in adipocytes in involuting IH. Using a combination of in vitro culture of patient-derived HemSCs and HemSCs implantation mouse models, we show that KLF2 governs the proliferation, apoptosis and cell cycle progression of HemSCs. Importantly, KLF2 acts as a crucial determinant of HemSCs' fate, directing their differentiation toward endothelial cells while inhibiting adipogenesis. Knockdown of KLF2 induces a pro-adipogenic transcriptome in HemSCs, leading to impaired blood vessel formation and accelerated adipocyte differentiation. Collectively, our findings highlight KLF2 as a critical regulator controlling the progression and involution of IH by modulating HemSCs' cell fate decisions.

Keywords: Differentiation; Hemangioma stem cells; Infantile hemangioma; KLF2; Transcription factors.