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人类 AGM 区域 HSCs 的巨大自我更新潜力在脐血中显著下降。

Vast Self-Renewal Potential of Human AGM Region HSCs Dramatically Declines in the Umbilical Cord Blood.

机构信息

Ontogeny of Haematopoietic Stem Cells Group, Institute for Stem Cell Research, MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, Scotland, UK; Department of Morphology, Institute of Anatomy and Anthropology, Riga Stradiņš University, Riga LV-1010, Latvia; School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.

Ontogeny of Haematopoietic Stem Cells Group, Institute for Stem Cell Research, MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, Scotland, UK.

出版信息

Stem Cell Reports. 2020 Oct 13;15(4):811-816. doi: 10.1016/j.stemcr.2020.08.008. Epub 2020 Sep 17.

DOI:10.1016/j.stemcr.2020.08.008
PMID:32946804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7561509/
Abstract

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.

摘要

人类造血干细胞(HSCs)在卡内基阶段 14-17 期间出现在主动脉-性腺-中肾(AGM)区域。虽然我们之前报道过这些 HSCs 可以产生不少于 300 个的子 HSCs,但它们的实际数量从未确定过。在这里,我们表明单个人类 AGM 区域 HSC 可以产生 600-1600 个功能上的子 HSCs。在一个案例中,CS 17 肝脏中的 HSCs 的存在为我们提供了一个独特的机会来描述肝定植后 HSC 自我更新潜力的降低。从临床角度来看,长期造血再生的效果取决于 HSC 的自我更新能力。我们定量地表明,与 AGM 区域的 HSCs 相比,这种能力在脐带血中显著下降。对第一个源自人类胚胎的 HSCs 巨大再生潜力的充分认识,为从多能干细胞生成临床上有用的 HSCs 设定了一个新的标准。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d2c/7561509/def3c9f501ad/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d2c/7561509/9cde36531c58/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d2c/7561509/def3c9f501ad/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d2c/7561509/9cde36531c58/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d2c/7561509/def3c9f501ad/gr2.jpg

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