Vast Self-Renewal Potential of Human AGM Region HSCs Dramatically Declines in the Umbilical Cord Blood.
Vast Self-Renewal Potential of Human AGM Region HSCs Dramatically Declines in the Umbilical Cord Blood.
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DOI：
10.1016/j.stemcr.2020.08.008
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发表时间：
2020-10-13
影响因子：
5.9
通讯作者：
Medvinsky A
中科院分区：
文献类型：
--
作者：
Ivanovs A;Rybtsov S;Anderson RA;Medvinsky A
人造血干细胞（hsc）在卡内基期（CS）出现在主动脉-性腺-中肾（AGM）区域14-17。虽然我们以前报道过这些造血干细胞可以产生不少于300个子造血干细胞，但它们的实际数量从未确定过。在这里，我们发现单个人类AGM区域的HSC可以产生600 - 1600个功能性的子HSC。在一个病例中，CS 17肝脏中存在HSC，这给了我们一个独特的机会来描述肝脏定植后HSC自我更新潜力的减少。从临床角度来看，长期造血再生的效果取决于造血干细胞的自我更新能力。我们定量地表明，与AGM地区的造血干细胞相比，脐带血的这种能力急剧下降。充分认识到第一批人类胚胎来源的造血干细胞的巨大再生潜力，为从多能干细胞中产生临床有用的造血干细胞树立了新的标准。单个人AGM区HSC可产生600 - 1600个功能完备的子HSC。在肝脏定植时，HSC的自我更新能力可能会下降。移植脐带血HSC的自我更新能力没有显著扩增。本研究为人类HSC的自我更新能力设定了新的标准。A. Medvinsky及其同事发现，胚胎主动脉-性腺-中肾区出现的第一批人造血干细胞（hsc）在移植到免疫功能低下的NSG小鼠体内后，可产生多达1600个功能性的子hsc。在脐带血造血干细胞中，第一批造血干细胞巨大的自我更新/再生潜力在胎儿发育结束时急剧下降。
Human hematopoietic stem cells (HSCs) emerge in the aorta-gonad-mesonephros (AGM) region during Carnegie stages (CS) 14–17. Although we previously reported that these HSCs can generate no less than 300 daughter HSCs, their actual number has never been established. Here, we show that a single human AGM region HSC can generate 600–1,600 functional daughter HSCs. The presence of HSCs in the CS 17 liver in one case gave us a unique opportunity to describe a reduction of HSC self-renewal potential after liver colonization. From a clinical perspective, the efficacy of long-term hematopoietic regeneration depends on HSC self-renewal capacity. We quantitatively show that this capacity dramatically declines in the umbilical cord blood compared with HSCs in the AGM region. A full appreciation of the vast regenerative potential of the first human embryo-derived HSCs sets a new bar for generation of clinically useful HSCs from pluripotent stem cells. A single human AGM region HSC can generate 600–1,600 fully functional daughter HSCs HSC self-renewal potential may decline by the time of liver colonization Transplanted umbilical cord blood HSCs self-renew without significant amplification This study sets a new bar for the self-renewal potential of human HSCs In this article, A. Medvinsky and colleagues show that the first human hematopoietic stem cells (HSCs) emerging in the embryonic aorta-gonad-mesonephros region can generate up to 1,600 functional daughter HSCs upon transplantation into immunocompromized NSG mice. The vast self-renewal/regeneration potential of the first HSCs dramatically drops by the end of fetal development in umbilical cord blood HSCs.
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影响因子：
158.5
作者：
GLUCKMAN, E;BROXMEYER, HE;BOYSE, EA
通讯作者：
BOYSE, EA
影响因子：
12.8
作者：
BOGGS, DR
通讯作者：
BOGGS, DR
DOI：
10.1126/science.1256337
发表时间：
2014-09-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fares I;Chagraoui J;Gareau Y;Gingras S;Ruel R;Mayotte N;Csaszar E;Knapp DJ;Miller P;Ngom M;Imren S;Roy DC;Watts KL;Kiem HP;Herrington R;Iscove NN;Humphries RK;Eaves CJ;Cohen S;Marinier A;Zandstra PW;Sauvageau G
通讯作者：
Sauvageau G
影响因子：
30.5
作者：
McKenzie, Joby L.;Gan, Olga I.;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
64.8
作者：
Wilkinson, Adam C.;Ishida, Reiko;Yamazaki, Satoshi
通讯作者：
Yamazaki, Satoshi