CD1d expression demarcates CDX4+ hemogenic mesoderm with definitive hematopoietic potential.
CD1d expression demarcates CDX4+ hemogenic mesoderm with definitive hematopoietic potential.
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CD1d表达将CDX4+造血中胚层与确定的造血潜能区分开来。
DOI：
10.1016/j.scr.2022.102808
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发表时间：
2022-07
影响因子：
1.2
通讯作者：
Sturgeon, Christopher M.
中科院分区：
文献类型：
--
作者：
Creamer, J. Philip;Luff, Stephanie A.;Yu, Hao;Sturgeon, Christopher M.
关键词：
早期hPSC分化的scRNAseq揭示了CDX 1/2/4+ CDld+中胚层群体。KDR + CD 1d+中胚层有效地产生具有红系、髓系和淋巴潜能的造血内皮。CD 1d衍生的CD 34+细胞强烈表达HOXA 7/9。为了实现人类多能干细胞（hPSC）向特定造血细胞类型的高效、可重复分化，需要全面了解所涉及的必要细胞信号传导和发育轨迹。先前的研究已经通过阶段特异性WNT和ACTIVIN/NODAL鉴定了胚胎外样和胚胎内样生血内皮（HE）的中胚层祖细胞，其中GYPA/GYPB（CD 235 a/B）表达作为仅具有胚胎外样生血潜能的中胚层的阳性选择标记。然而，一个积极的中胚层细胞表面标志物，专门胚胎内样生血潜力尚未确定。最近，我们报道了CDX 4的早期中胚层表达对最终HE特化具有重要调节作用，这表明CDX 4可能在造血发育过程中以细胞自主的方式起作用。为了鉴定CDX 4+中胚层，我们对hPSC衍生的中胚层培养物进行了单细胞（sc）RNAseq，揭示了表达CDX 4 hi的中胚层群体在非经典MHC-I类受体CD 1D中独特地富集。流式细胞术显示约60%的KDR+ CD 34-CD 235 a-中胚层是CD 1d+，并且CDX 4在CD 1d+中胚层中强烈富集。重要的是，只有CD 1d+中胚层含有CD 34 + HOXA+ HE，具有多系红细胞-骨髓-淋巴细胞潜能。因此，早期中胚层内的CDX 4 + CD 1d+表达界定了HE的早期祖细胞。这些见解可用于进一步研究人类造血发育和改善再生医学应用的造血分化条件。
scRNAseq of early hPSC differentiation reveals a CDX1/2/4+ CD1d + mesodermal population. KDR + CD1d + mesoderm efficiently gives rise to hemogenic endothelium with erythroid, myeloid, and lymphoid potential. CD1d-derived CD34 + cells robustly express HOXA7/9. To achieve efficient, reproducible differentiation of human pluripotent stem cells (hPSCs) towards specific hematopoietic cell-types, a comprehensive understanding of the necessary cell signaling and developmental trajectories involved is required. Previous studies have identified the mesodermal progenitors of extra-embryonic-like and intra-embryonic-like hemogenic endothelium (HE), via stage-specific WNT and ACTIVIN/NODAL, with GYPA/GYPB (CD235a/b) expression serving as a positive selection marker for mesoderm harboring exclusively extra-embryonic-like hemogenic potential. However, a positive mesodermal cell-surface marker with exclusively intra-embryonic-like hemogenic potential has not been identified. Recently, we reported that early mesodermal expression of CDX4 critically regulates definitive HE specification, suggesting that CDX4 may act in a cell-autonomous manner during hematopoietic development. To identify CDX4+ mesoderm, we performed single cell (sc)RNAseq on hPSC-derived mesodermal cultures, revealing CDX4hi expressing mesodermal populations were uniquely enriched in the non-classical MHC-Class-1 receptor CD1D. Flow cytometry demonstrated approximately 60% of KDR+CD34-CD235a- mesoderm was CD1d+, and CDX4 was robustly enriched within CD1d+ mesoderm. Critically, only CD1d+ mesoderm harbored CD34+ HOXA+ HE with multilineage erythroid-myeloid-lymphoid potential. Thus, CDX4+CD1d+ expression within early mesoderm demarcates an early progenitor of HE. These insights may be used for further study of human hematopoietic development and improve hematopoietic differentiation conditions for regenerative medicine applications.
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影响因子：
5.4
作者：
Alles J;Karaiskos N;Praktiknjo SD;Grosswendt S;Wahle P;Ruffault PL;Ayoub S;Schreyer L;Boltengagen A;Birchmeier C;Zinzen R;Kocks C;Rajewsky N
通讯作者：
Rajewsky N
人类多能干细胞定向分化确定性造血内皮和造血祖细胞
影响因子：
4.8
作者：
Ditadi, Andrea;Sturgeon, Christopher M.
通讯作者：
Sturgeon, Christopher M.
影响因子：
21.3
作者：
Ditadi A;Sturgeon CM;Tober J;Awong G;Kennedy M;Yzaguirre AD;Azzola L;Ng ES;Stanley EG;French DL;Cheng X;Gadue P;Speck NA;Elefanty AG;Keller G
通讯作者：
Keller G
影响因子：
64.8
作者：
Davidson, AJ;Ernst, P;Zon, LI
通讯作者：
Zon, LI
影响因子：
30.5
作者：
Schmitt, TM;de Pooter, RF;Zúñiga-Pflücker, JC
通讯作者：
Zúñiga-Pflücker, JC