Hyperleukocytic Acute Leukemia Circulating Exosomes Regulate HSCs and BM-MSCs

Hyperleukocytic acute leukemia (HLAL) circulating exosomes are delivered to hematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BM-MSCs), thereby inhibiting the normal hematopoietic process. In this paper, we have evaluated and explored the effects of miR-125b, which is carried b...

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Autores principales:	Yanmei Yang, Haiping He, Jigang He, Xuezhong Gu, Peng Hu, Rongxia Zuo, Yalian Sa
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Medicine (General) R5-920 Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/60b4a2b11eaf47ff9df0c1c0bdf1bc94
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spelling	oai:doaj.org-article:60b4a2b11eaf47ff9df0c1c0bdf1bc942021-11-29T00:56:49ZHyperleukocytic Acute Leukemia Circulating Exosomes Regulate HSCs and BM-MSCs2040-230910.1155/2021/9457070https://doaj.org/article/60b4a2b11eaf47ff9df0c1c0bdf1bc942021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/9457070https://doaj.org/toc/2040-2309Hyperleukocytic acute leukemia (HLAL) circulating exosomes are delivered to hematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BM-MSCs), thereby inhibiting the normal hematopoietic process. In this paper, we have evaluated and explored the effects of miR-125b, which is carried by HLAL-derived exosomes, on the hematopoietic function of HSCs and BM-MSCs. For this purpose, we have isolated exosomes from the peripheral blood of HLAL patients and healthy volunteers. Then, we measured the level of miR-125b in exosomes cocultured exosomes with HSCs and BM-MSCs. Moreover, we have used miR-125b inhibitors/mimic for intervention and then measured miR-125b expression and colony forming unit (CFU). Apart from it, HSC and BM-MSC hematopoietic-related factors α-globulin, γ-globulin, CSF2, CRTX4 and CXCL12, SCF, IGF1, and DKK1 expression were measured. Evaluation of the miR-125b and BAK1 targeting relationship, level of miR-125b, and expression of hematopoietic-related genes was performed after patients are treated with miR-125b mimic and si-BAK1. We have observed that miR-125b was upregulated in HLAL-derived exosomes. After HLAL-exosome acts on HSCs, the level of miR-125b is upregulated, reducing CFU and affecting the expression of α-globulin, γ-globulin, CSF2, and CRCX4. For BM-MSCs, after the action of HLAL-exo, the level of miR-125b is upregulated and affected the expression of CXCL12, SCF, IGF1, and DKK1. Exosomes derived from HLAL carry miR-125b to target and regulate BAK1. Further study confirmed that miR-125b and BAK1mimic reduced the expression of miR-125b and reversed the effect of miR-125b mimic on hematopoietic-related genes. These results demonstrated that HLAL-derived exosomes carrying miR-125b inhibit the hematopoietic differentiation of HSC and hematopoietic support function of BM-MSC through BAK1.Yanmei YangHaiping HeJigang HeXuezhong GuPeng HuRongxia ZuoYalian SaHindawi LimitedarticleMedicine (General)R5-920Medical technologyR855-855.5ENJournal of Healthcare Engineering, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920 Medical technology R855-855.5
spellingShingle	Medicine (General) R5-920 Medical technology R855-855.5 Yanmei Yang Haiping He Jigang He Xuezhong Gu Peng Hu Rongxia Zuo Yalian Sa Hyperleukocytic Acute Leukemia Circulating Exosomes Regulate HSCs and BM-MSCs
description	Hyperleukocytic acute leukemia (HLAL) circulating exosomes are delivered to hematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BM-MSCs), thereby inhibiting the normal hematopoietic process. In this paper, we have evaluated and explored the effects of miR-125b, which is carried by HLAL-derived exosomes, on the hematopoietic function of HSCs and BM-MSCs. For this purpose, we have isolated exosomes from the peripheral blood of HLAL patients and healthy volunteers. Then, we measured the level of miR-125b in exosomes cocultured exosomes with HSCs and BM-MSCs. Moreover, we have used miR-125b inhibitors/mimic for intervention and then measured miR-125b expression and colony forming unit (CFU). Apart from it, HSC and BM-MSC hematopoietic-related factors α-globulin, γ-globulin, CSF2, CRTX4 and CXCL12, SCF, IGF1, and DKK1 expression were measured. Evaluation of the miR-125b and BAK1 targeting relationship, level of miR-125b, and expression of hematopoietic-related genes was performed after patients are treated with miR-125b mimic and si-BAK1. We have observed that miR-125b was upregulated in HLAL-derived exosomes. After HLAL-exosome acts on HSCs, the level of miR-125b is upregulated, reducing CFU and affecting the expression of α-globulin, γ-globulin, CSF2, and CRCX4. For BM-MSCs, after the action of HLAL-exo, the level of miR-125b is upregulated and affected the expression of CXCL12, SCF, IGF1, and DKK1. Exosomes derived from HLAL carry miR-125b to target and regulate BAK1. Further study confirmed that miR-125b and BAK1mimic reduced the expression of miR-125b and reversed the effect of miR-125b mimic on hematopoietic-related genes. These results demonstrated that HLAL-derived exosomes carrying miR-125b inhibit the hematopoietic differentiation of HSC and hematopoietic support function of BM-MSC through BAK1.
format	article
author	Yanmei Yang Haiping He Jigang He Xuezhong Gu Peng Hu Rongxia Zuo Yalian Sa
author_facet	Yanmei Yang Haiping He Jigang He Xuezhong Gu Peng Hu Rongxia Zuo Yalian Sa
author_sort	Yanmei Yang
title	Hyperleukocytic Acute Leukemia Circulating Exosomes Regulate HSCs and BM-MSCs
title_short	Hyperleukocytic Acute Leukemia Circulating Exosomes Regulate HSCs and BM-MSCs
title_full	Hyperleukocytic Acute Leukemia Circulating Exosomes Regulate HSCs and BM-MSCs
title_fullStr	Hyperleukocytic Acute Leukemia Circulating Exosomes Regulate HSCs and BM-MSCs
title_full_unstemmed	Hyperleukocytic Acute Leukemia Circulating Exosomes Regulate HSCs and BM-MSCs
title_sort	hyperleukocytic acute leukemia circulating exosomes regulate hscs and bm-mscs
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/60b4a2b11eaf47ff9df0c1c0bdf1bc94
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Hyperleukocytic Acute Leukemia Circulating Exosomes Regulate HSCs and BM-MSCs

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