Analysis of function of microRNAs in Dlk1-Dio3 region in hematopoietic stem cells

造血干细胞Dlk1-Dio3区microRNA功能分析

• 批准号: 23791075
• 负责人: YAMAMOTO Ryo
• 金额: $ 2.66万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791075/
• 关键词: 造血幹細胞; 自己複製能; 多分化能; microRNA; 血液前駆細胞; 細胞系譜決定; 自己複製

Hematopoietic stem cells (HSCs, CD34-KSL) have self-renewal activity and multipotency. CD150+ cells in CD34-KSL fraction have long-term and myeloid-biased repopulating activity. We have identified microRNAs specific to CD150+CD34-KSL fraction and transplanted microRNA-transduced CD34-KSLs into lethally-irradiated mice. However, we could not detect microRNAs that expanded self-renewal activity. This is, in part, due to HSC heterogeneity because candidate microRNAs have been reported to be expressed in megakaryocytes. To assess this, we performed single-cell transplantation of bone marrows from mice in which all mature blood cells express fluorescent protein. We detected myeloid-restricted repopulating cells in addition to full-lineage HSC in HSC fraction, suggesting that some of candidate microRNAs have a role in lineage commitment rather than self-renewal.

造血干细胞（HSCs，CD 34-KSL）具有自我更新能力和多能性。CD 34-KSL组分中的CD 150+细胞具有长期和骨髓偏向的再增殖活性。我们已经鉴定了对CD 150 + CD 34-KSL组分特异性的microRNA，并将microRNA转导的CD 34-KSL移植到致死辐射的小鼠中。然而，我们无法检测到扩展自我更新活性的microRNA。这部分是由于HSC的异质性，因为已经报道了候选microRNA在巨核细胞中表达。为了评估这一点，我们进行了小鼠骨髓的单细胞移植，其中所有成熟的血细胞都表达荧光蛋白。我们在HSC组分中检测到除了全谱系HSC之外的骨髓限制性再生细胞，这表明一些候选microRNA在谱系定型而不是自我更新中起作用。

项目成果

Earliest lineage commitment in hematopoietic stem cells

造血干细胞最早的谱系定型

• 发表时间: 2015
• 作者: Ghosn EE;Yamamoto R;Hamanaka S;Yang Y;Herzenberg LA;Nakauchi H;Herzenberg LA.;Yuhei Kamada;Kenichi Yoshida;加藤貴康;Ryo Yamamoto
• 通讯作者: Ryo Yamamoto

Frequent pathway mutations of splicing machinery in myelodysplasia

• DOI: 10.1038/nature10496
• 发表时间: 2011-10-06
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Yoshida, Kenichi;Sanada, Masashi;Ogawa, Seishi
• 通讯作者: Ogawa, Seishi

In vivo clonal analysis of hematopoietic stem cells unveils novel non-stepwise differentiation pathways,

造血干细胞的体内克隆分析揭示了新的非逐步分化途径，

• 发表时间: 2013
• 作者: Ghosn EE;Yamamoto R;Hamanaka S;Yang Y;Herzenberg LA;Nakauchi H;Herzenberg LA.;Yuhei Kamada;Kenichi Yoshida;加藤貴康;Ryo Yamamoto;Takayasu Kato;山本玲;Hideharu Muto;Ryo Yamamoto
• 通讯作者: Ryo Yamamoto

Megakaryocyte lineage commitment in hematopoietic stem cells

造血干细胞中的巨核细胞谱系定型

• 发表时间: 2011
• 作者: Ryo Yamamoto;Yohei Morita;Hideo Ema;Jun Ooehara;Sanae Hamanaka;Masafumi Onodera;Hiromitsu Nakauchi
• 通讯作者: Hiromitsu Nakauchi

Ryo Yamamoto, Yohei Morita, Sanae Hamanaka, Masafumi Onodera and Hideo Ema, Hiromitsu Nakauchi

山本亮、森田阳平、滨中早苗、小野寺雅文、江间秀雄、中内弘光

• 发表时间: 2011
• 作者: Ryo Yamamoto;Yohei Morita;Hideo Ema;Jun Ooehara;Sanae Hamanaka;Masafumi Onodera;Hiromitsu Nakauchi;Takayasu Kato;The earliest lineage commitment in hematopoietic stem cells
• 通讯作者: The earliest lineage commitment in hematopoietic stem cells