Variable SATB1 Levels Regulate Hematopoietic Stem Cell Heterogeneity with Distinct Lineage Fate
Variable SATB1 Levels Regulate Hematopoietic Stem Cell Heterogeneity with Distinct Lineage Fate
复制标题
DOI：
10.1016/j.celrep.2018.05.042
复制
发表时间：
2018-06-12
期刊：
影响因子：
8.8
通讯作者：
Kanakura, Yuzuru
中科院分区：
文献类型：
--
作者：
Doi, Yukiko;Yokota, Takafumi;Kanakura, Yuzuru
造血干细胞（HSCs）是一个具有自我更新和分化能力的异质性细胞群，然而维持这种异质性的机制尚不清楚。在这里，我们表明，SATB 1参与调节HSC异质性。在条件Satb 1基因敲除小鼠的结果表明，SATB 1是重要的自我更新和淋巴细胞的成体HSC。此外，基于SATB 1/Tomato强度对来自Satb 1/Tomato敲入报告小鼠的HSC进行分类，移植实验揭示了向淋巴细胞谱系的更强分化，沿着高SATB 1水平，而SATB 1（-）HSC遵循髓系谱系，与全基因组转录和细胞培养研究一致。重要的是，SATB 1（-）和SATB 1（+）HSC群体在移植后可相互转化，SATB 1（+）HSC在初次受体中相对于SATB 1（-）HSC表现出更高的重建和淋巴细胞生成潜力，而两种HSC在二次受体中表现出同样有效的重建造血干细胞。这些结果表明，SATB 1水平调节HSC多能性的维持，其变化有助于HSC异质性。
Hematopoietic stem cells (HSCs) comprise a heterogeneous population exhibiting self-renewal and differentiation capabilities; however, the mechanisms involved in maintaining this heterogeneity remain unclear. Here, we show that SATB1 is involved in regulating HSC heterogeneity. Results in conditional Satb1-knockout mice revealed that SATB1 was important for the self-renewal and lymphopoiesis of adult HSCs. Additionally, HSCs from Satb1/Tomato-knockin reporter mice were classified based on SATB1/Tomato intensity, with transplantation experiments revealing stronger differentiation toward the lymphocytic lineage along with high SATB1 levels, whereas SATB1(-) HSCs followed the myeloid lineage in agreement with genome-wide transcription and cell culture studies. Importantly, SATB1(-) and SATB1(+) HSC populations were interconvertible upon transplantation, with SATB1(+) HSCs showing higher reconstituting and lymphopoietic potentials in primary recipients relative to SATB1(-) HSCs, whereas both HSCs exhibited equally efficient reconstituted lym-pho-hematopoiesis in secondary recipients. These results suggest that SATB1 levels regulate the maintenance of HSC multipotency, with variations contributing to HSC heterogeneity.