Changes in histidine decarboxylase expression influence extramedullary hematopoiesis in postnatal mice
Changes in histidine decarboxylase expression influence extramedullary hematopoiesis in postnatal mice
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组氨酸脱羧酶表达变化影响产后小鼠髓外造血
DOI：
10.1002/ar.24533
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Soeta Satoshi
中科院分区：
文献类型：
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作者：
Otsuka Hirotada;Endo Yasuo;Ohtsu Hiroshi;Inoue Satoshi;Kuraoka Mutsuki;Koh Miki;Yagi Hideki;Nakamura Masanori;Soeta Satoshi
组氨酸脱羧酶（HDC），即组胺合成酶，在造血干细胞和骨髓中具有谱系承诺的祖细胞（BM）中表达。然而，组胺在造血中的作用并没有得到很好的描述。为了评估组胺在造血中的作用，我们分析了2周、3周和6周大的野生型小鼠造血部位、BM、脾脏和肝脏中HDC表达的变化。我们还使用HDC‐缺失（HDC‐KO）小鼠对造血部位进行了形态学分析。在野生型成人中，HDC在BM中的表达高于脾脏和肝脏，并呈年龄依赖性增加。组织学分析显示，与野生型小鼠相比，HDC‐KO小鼠的成年BM和脾脏没有明显变化。在肝脏中，HDC表达在3周龄时暂时升高，在6周龄时下降。形态学分析显示，在2周龄和3周龄时，HDC‐KO小鼠的肝脏比野生型小鼠有更多的造血集落和巨核细胞，而在成年小鼠中没有观察到任何变化。这些造血集落大多由B220阳性B淋巴细胞和TER119阳性红母细胞组成，细胞增殖标志物PCNA阳性。值得注意的是，在N -乙酰组胺处理下，HDC‐KO小鼠的这些造血菌落下降。与野生型小鼠相比，3周龄的HDC‐KO小鼠肝脏中造血相关细胞因子Il3、Il7、Epo、Gcsf和cxcl12mrna的表达显著增加。这些结果表明，组胺缺乏可能通过调节出生后小鼠肝脏中造血相关细胞因子的表达来维持一个适合造血的微环境。
Histidine decarboxylase (HDC), histamine synthase, is expressed in hematopoietic stem cells and in lineage‐committed progenitors in the bone marrow (BM). However, the role of histamine in hematopoiesis is not well described. To evaluate the role of histamine in hematopoiesis, we analyzed the changes in HDC expression at hematopoietic sites, the BM, spleen, and liver of 2‐, 3‐, and 6‐week‐old wild‐type mice. We also performed morphological analyses of the hematopoietic sites using HDC‐deficient (HDC‐KO) mice. In wild‐type adults, HDC expression in the BM was higher than that in the spleen and liver and showed an age‐dependent increase. Histological analysis showed no significant change in the adult BM and spleen of HDC‐KO mice compared to wild‐type mice. In the liver, HDC expression was temporarily increased at 3 weeks and decreased at 6 weeks of age. Morphological analysis of the liver revealed more numerous hematopoietic colonies and megakaryocytes in HDC‐KO mice compared to wild‐type mice at 2 and 3 weeks of age, whereas no changes were observed in adults. Most of these hematopoietic colonies consisted of B220‐positive B‐lymphocytes and TER119‐positive erythroblasts and were positive for the cell proliferation marker PCNA. Notably, these hematopoietic colonies declined in HDC‐KO mice upon N‐acetyl histamine treatment. A significant increase in the expression of hematopoiesis‐related cytokines,Il3,Il7,Epo,Gcsf, andCxcl12mRNA was observed in the liver of 3‐week‐old HDC‐KO mice compared to wild‐type mice. These results suggest that histamine‐deficiency may maintain an microenvironment suitable for hematopoiesis by regulating hematopoiesis‐related cytokine expression in the liver of postnatal mice.