Prospective isolation of mouse and human hematopoietic stem cells using PLXDC2
Year: 2025
Type: article
Abstract: Numerous strategies exist to isolate hematopoietic stem cells (HSCs) using complex combinations of markers and flow cytometry. However, robust identification of HSCs using imaging techniques is substantially more challenging which has prompted the recent development of HSC reporter mice. To date, none of the molecules used in these reporters have been useful for human HSC identification. Here we report that PLXDC2 is a useful marker for both mouse and human HSCs. Using a green fluorescent protein (GFP) knock-in at the Plxdc2 locus in mice (hereafter denoted as Plxdc2 -GFP), we showed that Plxdc2 -GFP is highly expressed in HSCs with 1 in 2.8 Plxdc2 -GFP + CD150 + cells giving long-term multi-lineage reconstitution in transplantation. Moreover, we developed a novel human PLXDC2 antibody and showed that human PLXDC2 + HSCs have stronger long-term multilineage reconstitution ability compared with PLXDC2 - HSCs in a xenograft model. Thus, our study identifies PLXDC2 as a highly relevant molecule in HSC identification, potentially allowing greater purity and live in vivo tracking of these cells.
Source: Communications Biology
Authors: Yosuke Tanaka, Yasushi Kubota, Riko Kikuchi, Tomohiro Yabushita, Takaharu Kimura, Ivo Lieberam, Jillian L. Barlow, Josh W. Bramley, Tsuyoshi Fukushima, Chiaki Sakuma, Takashi Shibata, Masataka Nakagawa, Yasunori Kurosawa, Toshiaki Maruyama, C. J. Okumura, Yuichiro Arima, Yoshinori Sato, Yasuo Ono, Teruo Akuta, Hidenobu Mizuno, David G. Kent, Thomas M. Jessell, Susumu Goyama, Hidekazu Nishikii, Shinya Kimura, Satoshi Yamazaki, Toshio Suda, Toshio Kitamura
Institutions: Institute of Medical Science, The University of Tokyo, International Research Center for Medical Sciences, Kumamoto University, The University of Tokyo, Kumamoto University, Saga University, Saga-Ken Medical Centre Koseikan, University of Tsukuba, King's College London, University of York, Kyokuto Pharmaceutical Industrial Co., Ltd. (Japan), Teikyo University, Teikyo Heisei University, Howard Hughes Medical Institute, Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: Japan Agency for Medical Research and Development, Teikyo University School of Medicine, Tokyo Metropolitan Small and Medium Enterprise Support Center, King's College London, Ministry of Education, Culture, Sports, Science and Technology, University of Tokyo, University of Tsukuba, SENSHIN Medical Research Foundation, Medical Research Council Centre for Neurodevelopmental Disorders, Medical Research Council, Japan Society for the Promotion of Science, Institute of Medical Science, University of Tokyo, Graduate School of Frontier Sciences, University of Tokyo
Awards: G137464505, G2002465135, Human blood stem cell expansion: Empowering new technology for stem cell medicine, CRISPR/Cas9-mediated base-editing enables a chain reaction through sequential repair of sgRNA scaffold mutations, G8005977170, Development of a treatment strategy for leukemia using a novel oligonucleotide therapeutics technology and folate-appended cyclodextrin, Maintenance of multipotency of hematopoietic stem cells and distribution of midbody
OpenAlex ID: W4417200701