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研究揭示人类胎儿骨髓的血液和免疫发育
作者:小柯机器人 发布时间:2021/10/9 13:52:19

英国纽卡斯尔大学Muzlifah Haniffa小组揭示人类胎儿骨髓的血液和免疫发育。2021年9月29日,《自然》杂志在线发表了这项成果。

据研究人员介绍,骨髓(BM)中的造血功能维持着整个产后生命的血液和免疫细胞的生成。人类骨髓的造血功能在受孕后11-12周首次出现,但对于胎儿骨髓(FBM)如何演变来满足胎儿和新生儿的高度特化需求几乎一无所知。

研究人员利用mRNA和多重蛋白表位表达的多组学评估详细介绍了FBM的发育。研究人员发现,完整的血液和免疫细胞库是在第二胎早期6-7周的短暂时间内在FBM中建立起来的。FBM促进了骨髓细胞的快速和广泛的多样化,粒细胞、嗜酸性细胞和树突状细胞亚群首次出现。B淋巴细胞在FBM中的大量扩增与相同胎龄的胎儿肝脏形成对比。胎儿肝脏、FBM和脐带血的造血祖细胞表现出转录和功能差异,有助于组织特异性和细胞多样化。内皮细胞类型形成了不同的血管结构,研究人员发现在FBM内有区域性的分隔。

最后,研究人员揭示了B淋巴细胞、红细胞和骨髓细胞发育的选择性破坏,这是由于唐氏综合征(21三体)的细胞内分化偏向以及通过改变微环境的外在调节。

附:英文原文

Title: Blood and immune development in human fetal bone marrow and Down syndrome

Author: Jardine, Laura, Webb, Simone, Goh, Issac, Quiroga Londoo, Mariana, Reynolds, Gary, Mather, Michael, Olabi, Bayanne, Stephenson, Emily, Botting, Rachel A., Horsfall, Dave, Engelbert, Justin, Maunder, Daniel, Mende, Nicole, Murnane, Caitlin, Dann, Emma, McGrath, Jim, King, Hamish, Kucinski, Iwo, Queen, Rachel, Carey, Christopher D., Shrubsole, Caroline, Poyner, Elizabeth, Acres, Meghan, Jones, Claire, Ness, Thomas, Coulthard, Rowen, Elliott, Natalina, OByrne, Sorcha, Haltalli, Myriam L. R., Lawrence, John E., Lisgo, Steven, Balogh, Petra, Meyer, Kerstin B., Prigmore, Elena, Ambridge, Kirsty, Jain, Mika Sarkin, Efremova, Mirjana, Pickard, Keir, Creasey, Thomas, Bacardit, Jaume, Henderson, Deborah, Coxhead, Jonathan, Filby, Andrew, Hussain, Rafiqul, Dixon, David, McDonald, David, Popescu, Dorin-Mirel, Kowalczyk, Monika S., Li, Bo, Ashenberg, Orr, Tabaka, Marcin, Dionne, Danielle, Tickle, Timothy L., Slyper, Michal, Rozenblatt-Rosen, Orit, Regev, Aviv, Behjati, Sam, Laurenti, Elisa, Wilson, Nicola K., Roy, Anindita, Gttgens, Berthold, Roberts, Irene, Teichmann, Sarah A., Haniffa, Muzlifah

Issue&Volume: 2021-09-29

Abstract: Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11–12 weeks after conception1,2, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialized needs of the fetus and newborn. Here we detail the development of FBM, including stroma, using multi-omic assessment of mRNA and multiplexed protein epitope expression. We find that the full blood and immune cell repertoire is established in FBM in a short time window of 6–7 weeks early in the second trimester. FBM promotes rapid and extensive diversification of myeloid cells, with granulocytes, eosinophils and dendritic cell subsets emerging for the first time. The substantial expansion of B lymphocytes in FBM contrasts with fetal liver at the same gestational age. Haematopoietic progenitors from fetal liver, FBM and cord blood exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we show are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B lymphocyte, erythroid and myeloid development owing to a cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21).

DOI: 10.1038/s41586-021-03929-x

Source: https://www.nature.com/articles/s41586-021-03929-x

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html