TGFBI Expressed by Bone Marrow Niche Cells and Hematopoietic Stem and Progenitor Cells Regulates Hematopoiesis.
TGFBI Expressed by Bone Marrow Niche Cells and Hematopoietic Stem and Progenitor Cells Regulates Hematopoiesis.
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DOI：
10.1089/scd.2018.0124
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发表时间：
2018-11-01
影响因子：
4
通讯作者：
Voermans C
中科院分区：
文献类型：
--
作者：
Klamer SE;Dorland YL;Kleijer M;Geerts D;Lento WE;van der Schoot CE;von Lindern M;Voermans C
造血干细胞和祖细胞（HSPC）与细胞外基质（ECM）组分和来自骨髓（BM）微环境的细胞的相互作用控制其稳态。再生BM条件可以诱导ECM蛋白转化生长因子β诱导的基因H3（TGFBI或BIGH 3）在鼠HSPC中的表达。在这项研究中，我们研究了TGFBI在人HSPC和BM间充质基质细胞（MSC）中表达的增加或减少如何影响HSPC的维持，分化和迁移。过表达TGFBI的HSPCs表现出加速的巨核细胞生成，而粒细胞、红细胞和单核细胞培养物的粒细胞分化和增殖减少。此外，TGFBI表达的上调和下调均损害HSPC的HSPC集落形成能力。有趣的是，具有降低的TGFBI水平的HSPC的集落形成能力在与MSC长期共培养后增加，如通过长期培养集落形成细胞（LTC-CFC）形成所测量的。此外，HSPC中的TGFBI下调导致鹅卵石区域形成细胞（CAFC）频率增加，这是造血干细胞（HSC）能力的量度。一致地，HSPC中TGFBI上调导致CAFC和LTC-CFC频率降低。这些结果表明，HSPC中降低的TGFBI水平增强了HSC的维持，但仅在MSC存在的情况下。此外，MSC中TGFBI水平降低影响MSC/HSPC相互作用，如通过HSPC在基质层下的迁移增加所观察到的。总之，BM龛中TGFBI表达的严格调节对于平衡HSPC增殖和分化是必需的。
The interactions of hematopoietic stem and progenitor cells (HSPCs) with extracellular matrix (ECM) components and cells from the bone marrow (BM) microenvironment control their homeostasis. Regenerative BM conditions can induce expression of the ECM protein transforming growth factor beta-induced gene H3 (TGFBI or BIGH3) in murine HSPCs. In this study, we examined how increased or reduced TGFBI expression in human HSPCs and BM mesenchymal stromal cells (MSCs) affects HSPC maintenance, differentiation, and migration. HSPCs that overexpressed TGFBI showed accelerated megakaryopoiesis, whereas granulocyte differentiation and proliferation of granulocyte, erythrocyte, and monocyte cultures were reduced. In addition, both upregulation and downregulation of TGFBI expression impaired HSPC colony-forming capacity of HSPCs. Interestingly, the colony-forming capacity of HSPCs with reduced TGFBI levels was increased after long-term co-culture with MSCs, as measured by long-term culture-colony forming cell (LTC-CFC) formation. Moreover, TGFBI downregulation in HSPCs resulted in increased cobblestone area-forming cell (CAFC) frequency, a measure for hematopoietic stem cell (HSC) capacity. Concordantly, TGFBI upregulation in HSPCs resulted in a decrease of CAFC and LTC-CFC frequency. These results indicate that reduced TGFBI levels in HSPCs enhanced HSC maintenance, but only in the presence of MSCs. In addition, reduced levels of TGFBI in MSCs affected MSC/HSPC interaction, as observed by an increased migration of HSPCs under the stromal layer. In conclusion, tight regulation of TGFBI expression in the BM niche is essential for balanced HSPC proliferation and differentiation.
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影响因子：
5.9
作者：
Gazit, Roi;Garrison, Brian S.;Rao, Tata Nageswara;Shay, Tal;Costello, James;Ericson, Jeff;Kim, Francis;Collins, James J.;Regev, Aviv;Wagers, Amy J.;Rossi, Derrick J.
通讯作者：
Rossi, Derrick J.
影响因子：
11.2
作者：
Becker, Juergen;Erdlenbruch, Bernhard;Schweigerer, Lothar
通讯作者：
Schweigerer, Lothar
影响因子：
3.1
作者：
Morita, N;Yamamoto, M;Tanizawa, T
通讯作者：
Tanizawa, T
影响因子：
2.6
作者：
Hevehan, DL;Papoutsakis, ET;Miller, WM
通讯作者：
Miller, WM
影响因子：
23.9
作者：
Anjos-Afonso, Fernando;Currie, Erin;Bonnet, Dominique
通讯作者：
Bonnet, Dominique