Blood and immune development in human fetal bone marrow and Down syndrome.
Blood and immune development in human fetal bone marrow and Down syndrome.
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DOI：
10.1038/s41586-021-03929-x
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发表时间：
2021-10
期刊：
影响因子：
64.8
通讯作者：
Haniffa M
中科院分区：
文献类型：
--
作者：
Jardine L;Webb S;Goh I;Quiroga Londoño M;Reynolds G;Mather M;Olabi B;Stephenson E;Botting RA;Horsfall D;Engelbert J;Maunder D;Mende N;Murnane C;Dann E;McGrath J;King H;Kucinski I;Queen R;Carey CD;Shrubsole C;Poyner E;Acres M;Jones C;Ness T;Coulthard R;Elliott N;O'Byrne S;Haltalli MLR;Lawrence JE;Lisgo S;Balogh P;Meyer KB;Prigmore E;Ambridge K;Jain MS;Efremova M;Pickard K;Creasey T;Bacardit J;Henderson D;Coxhead J;Filby A;Hussain R;Dixon D;McDonald D;Popescu DM;Kowalczyk MS;Li B;Ashenberg O;Tabaka M;Dionne D;Tickle TL;Slyper M;Rozenblatt-Rosen O;Regev A;Behjati S;Laurenti E;Wilson NK;Roy A;Göttgens B;Roberts I;Teichmann SA;Haniffa M
骨髓（BM）中的造血维持整个出生后生命的血液和免疫细胞的产生。造血在受孕后11-12周首次出现在人类BM中，但几乎不知道胎儿BM（FBM）如何进化以满足胎儿和新生儿的高度专业化需求。在这里，我们详细介绍了FBM的发展，包括基质，使用多组学评估的mRNA和多重蛋白表位表达。我们发现，完整的血液和免疫细胞库是建立在FBM在6-7周的短时间窗口早期在第二个三个月。FBM促进骨髓细胞的快速和广泛的多样化，粒细胞，嗜酸性粒细胞和树突状细胞亚群首次出现。在相同胎龄时，FBM与FL相比，B淋巴细胞大量扩增。来自FL、FBM和脐带血（CB）的造血祖细胞表现出有助于组织特异性身份和细胞多样化的转录和功能差异。内皮细胞类型形成不同的血管结构，我们证明了FBM内的区域划分。最后，我们揭示了选择性破坏B淋巴细胞，红细胞和骨髓细胞的发展，由于细胞的内在分化的偏见，以及通过改变唐氏综合征（21三体）的微环境的外在调节。
Haematopoiesis in the bone marrow (BM) maintains blood and immune cell production throughout postnatal life. Haematopoiesis first emerges in human BM at 11-12 post conception weeks, yet almost nothing is known about how fetal BM (FBM) evolves to meet the highly specialised 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. Substantial B-lymphocyte expansion in FBM contrasts with FL at the same gestational age. Haematopoietic progenitors from FL, FBM and cord blood (CB) exhibit transcriptional and functional differences that contribute to tissue-specific identity and cellular diversification. Endothelial cell types form distinct vascular structures that we demonstrate are regionally compartmentalized within FBM. Finally, we reveal selective disruption of B-lymphocyte, erythroid and myeloid development due to cell-intrinsic differentiation bias as well as extrinsic regulation through an altered microenvironment in Down syndrome (trisomy 21).
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影响因子：
64.8
作者：
Mullighan, Charles G.;Goorha, Salil;Downing, James R.
通讯作者：
Downing, James R.
影响因子：
15.9
作者：
LONG, MW;BRIDDELL, R;HOFFMAN, R
通讯作者：
HOFFMAN, R
影响因子：
64.8
作者：
Kusumbe AP;Ramasamy SK;Adams RH
通讯作者：
Adams RH
影响因子：
168.9
作者：
Wiemels, JL;Cazzaniga, G;Greaves, MF
通讯作者：
Greaves, MF
DOI：
10.1073/pnas.0611177104
发表时间：
2007-02-27
影响因子：
11.1
作者：
Suchting, Steven;Freitas, Catarina;Eichmann, Anne
通讯作者：
Eichmann, Anne