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通过转录因子富集区分CB-和LPB-CD34细胞在人源化小鼠中的不同再增殖活性。

Distinct Repopulation Activity in Hu-Mice Between CB- and LPB-CD34 Cells by Enrichment of Transcription Factors.

作者信息

Han A-Reum, Lee Jeong Eun, Lee Min Ji, Ko Seung Young, Shin Hyun Soo, Lee Ji Yoon, Lee Dong Ryul

机构信息

Department of Biomedical Science, CHA University, Seongnam, Korea.

CHA Advanced Research Institute, CHA Bundang Medical Center, CHA University, Seongnam, Korea.

出版信息

Int J Stem Cells. 2021 May 30;14(2):203-211. doi: 10.15283/ijsc21015.

DOI:10.15283/ijsc21015
PMID:33906982
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8138658/
Abstract

BACKGROUND AND OBJECTIVES

Human CD34 hematopoietic stem cells can reconstitute the human hematopoietic system when transplanted into immunocompromised mice after irradiation. Human leukapheresis peripheral blood (LPB)- and cord blood (CB)-derived CD34 cells have a similar capacity to reconstitute myeloid lineage cells in a humanized mice (hu-mice) model. However, potent stem cells, such as CB-CD34 cells, efficiently reconstitute the lymphoid system in vivo compared to LPB-CD34 cells. Modeling the human hematolymphoid system is vital for studying immune cell crosstalk in human xenografted mice, with CB-CD34 cells used as an optimized cell source because they are essential in reconstituting lymphoid lineage cells.

METHODS AND RESULTS

In this study, we established hu-mice that combined human characteristics with long-term survival and investigated the efficiency of the engraftment of lymphoid lineage cells derived from LPB- and CB-CD34 cells in the bone marrow, spleen, and LPB. We found an overall increase in the transcriptional activity of lymphoid lineage genes in CB-CD34 cells. Our results revealed that potent CB-CD34 cells displaying a general upregulation of the expression of genes involved in lymphopoiesis could contribute to the hematolymphoid system in the humanized mice model with longevity.

CONCLUSIONS

Our data suggest that humanized mouse model by usage of CB-CD34 cells displaying high expression of TFs for lymphoid lineage cells can contribute to study the immune response against lymphocytes.

摘要

背景与目的

人类CD34造血干细胞在照射后移植到免疫缺陷小鼠体内时，可重建人类造血系统。人白细胞单采外周血（LPB）和脐血（CB）来源的CD34细胞在人源化小鼠（hu-小鼠）模型中具有相似的重建髓系细胞的能力。然而，与LPB-CD34细胞相比，诸如CB-CD34细胞等强大的干细胞在体内能更有效地重建淋巴系统。建立人类血液淋巴系统模型对于研究人源化小鼠中免疫细胞的相互作用至关重要，CB-CD34细胞因其在重建淋巴系细胞中不可或缺而被用作优化的细胞来源。

方法与结果

在本研究中，我们建立了具有人类特征且能长期存活的hu-小鼠，并研究了LPB-和CB-CD34细胞来源的淋巴系细胞在骨髓、脾脏和LPB中的植入效率。我们发现CB-CD34细胞中淋巴系基因的转录活性总体增加。我们的结果表明，显示参与淋巴细胞生成的基因表达普遍上调的强大CB-CD34细胞可在具有长期存活能力的人源化小鼠模型中促进血液淋巴系统的形成。

结论

我们的数据表明，使用对淋巴系细胞显示高表达转录因子的CB-CD34细胞构建的人源化小鼠模型有助于研究针对淋巴细胞的免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f387/8138658/4422c0fd2813/ijsc-14-2-203-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f387/8138658/4acab7041764/ijsc-14-2-203-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f387/8138658/5d8f750e8b86/ijsc-14-2-203-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f387/8138658/4422c0fd2813/ijsc-14-2-203-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f387/8138658/4acab7041764/ijsc-14-2-203-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f387/8138658/5d8f750e8b86/ijsc-14-2-203-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f387/8138658/4422c0fd2813/ijsc-14-2-203-f3.jpg

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