演題詳細

ポスター / Poster

ポスター 38 (Poster 38) :血栓症・その他 (Thrombosis and Others)

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日程
2013年10月11日(金)
時間
16:50 - 17:50
会場
ポスター会場 / Poster (ロイトン札幌 3F ロイトンホールABCD)
座長・司会
小嶋 哲人 (Tetsuhito Kojima):1
1:名古屋大学大学院医学系研究科
 
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TPO/cMpl-dependent megakaryocyte lineage decision at the proximity of hematopoietic stem cells

演題番号 : PS-1-286

金沢 陽介 (Yosuke Kanazawa):1、錦井 秀和 (Hidekazu Nishikii):1、松下 賢司 (Kenji Matsushita):1、梅本 晃正 (Terumasa Umemoto):2、松崎 優 (Yu Matsuzaki):2、加藤 貴康 (Takayasu Kato):1、坂田(柳元) 麻実子 (Mamiko Sakata-Yanagimoto):1、大和 雅之 (Masayuki Yamato):2、千葉 滋 (Shigeru Chiba):1

1:Department of Hematology, Faculty of Medicine, University of Tsukuba, Japan、2:Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University

 

Megakaryocytes (Meg) are mapped at the downstream of bilineage progenitors for erythroid and Meg (MEP), whereas the bifurcation of a Meg differentiation pathway at the proximity of hematopoietic stem cells (HSC) is also postulated. Indeed, HSC and Meg share several features, such as surface markers, transcription factors, and cytokine signaling, particularly that through thrombopoietin (TPO)/cMpl, which is crucial for the maintenance of HSC and Meg differentiation. Here, we investigated the pathway for Meg differentiation using liquid culture, FACS, and single cell PCR. We found that 6.3-6.9% of the Lin-c-Kit+Sca1-CD34+CD16/32low progenitor cells expressed GPIba, which has been considered as a mature Meg marker. In liquid culture, they were differentiated exclusively to Meg (34a-MKP). GPIba+ cells were not detected by FACS in the KSL population at the steady state. However, single cell PCR revealed that mRNA for both GPIba and vWF was expressed in a CD41+KSL population. Only very minor cells from MEP expressed these Meg lineage-specific genes. Moreover, the GPIba+ cells became detectable in the CD41+KSL population by FACS during the recovery phase after 5-FU treatment. We also investigated the TPO dependency for 34a+MKP and MEP generation using cMpl-deficient mice. The frequencies of both CD41+KSL and 34a+MKP were markedly reduced compared with that of MEP. As a summary, our observations imply that the fate decision of Meg lineage could be made at the proximity of HSC and the pathway through CD41+KSL/34a+MKP is highly TPO/cMpl dependent.

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