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α1,3-岩藻糖基化处理可改善脐血CD34阴性造血干细胞的归巢。

α1,3-fucosylation treatment improves cord blood CD34 negative hematopoietic stem cell navigation.

作者信息

Al-Amoodi Asma S, Kai Jing, Li Yanyan, Malki Jana S, Alghamdi Abdullah, Al-Ghuneim Arwa, Saera-Vila Alfonso, Habuchi Satoshi, Merzaban Jasmeen S

机构信息

Bioscience Program, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Kingdom of Saudi Arabia.

Sequentia Biotech SL, Barcelona, Spain.

出版信息

iScience. 2024 Jan 12;27(2):108882. doi: 10.1016/j.isci.2024.108882. eCollection 2024 Feb 16.

DOI:10.1016/j.isci.2024.108882
PMID:38322982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10845921/
Abstract

For almost two decades, clinicians have overlooked the diagnostic potential of CD34 hematopoietic stem cells because of their limited homing capacity relative to CD34HSCs when injected intravenously. This has contributed to the lack of appeal of using umbilical cord blood in HSC transplantation because its stem cell count is lower than bone marrow. The present study reveals that the homing and engraftment of CD34HSCs can be improved by adding the Sialyl Lewis X molecule via α1,3-fucosylation. This unlocks the potential for using this more primitive stem cell to treat blood disorders because our findings show CD34HSCs have the capacity to regenerate cells in the bone marrow of mice for several months. Furthermore, our RNA sequencing analysis revealed that CD34HSCs have unique adhesion pathways, downregulated in CD34HSCs, that facilitate interaction with the bone marrow niche. Our findings suggest that CD34 cells will best thrive when the HSC resides in its microenvironment.

摘要

近二十年来，临床医生一直忽视CD34造血干细胞的诊断潜力，因为静脉注射时，相对于CD34造血干细胞，其归巢能力有限。这导致脐带血在造血干细胞移植中缺乏吸引力，因为其干细胞数量低于骨髓。本研究表明，通过α1,3-岩藻糖基化添加唾液酸化路易斯X分子，可以改善CD34造血干细胞的归巢和植入。这开启了使用这种更原始的干细胞治疗血液疾病的可能性，因为我们的研究结果表明，CD34造血干细胞有能力在小鼠骨髓中再生细胞达数月之久。此外，我们的RNA测序分析显示，CD34造血干细胞具有独特的黏附途径，在CD34造血干细胞中下调，有助于与骨髓生态位相互作用。我们的研究结果表明，当造血干细胞位于其微环境中时，CD34细胞将最易茁壮成长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/85d393a4cd05/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/4319ea450ced/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/1331a2931af1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/42cbdf97ae41/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/cf0d2fc7ad42/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/0995c07d8d8f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/947be52cb899/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/faf3cae24d21/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/85d393a4cd05/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/4319ea450ced/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/1331a2931af1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/42cbdf97ae41/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/cf0d2fc7ad42/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/0995c07d8d8f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/947be52cb899/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/faf3cae24d21/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef9e/10845921/85d393a4cd05/gr7.jpg

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