Single Cell RNA-Seq Analysis of Human Red Cells.
Single Cell RNA-Seq Analysis of Human Red Cells.
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DOI：
10.3389/fphys.2022.828700
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发表时间：
2022
影响因子：
4
通讯作者：
Chi, Jen-Tsan
中科院分区：
文献类型：
--
作者：
Jain, Vaibhav;Yang, Wen-Hsuan;Wu, Jianli;Roback, John D.;Gregory, Simon G.;Chi, Jen-Tsan
人类红细胞（RBC）或红细胞是负责气体交换的最丰富的血细胞。RBC疾病影响数亿人，并造成巨大的经济和个人负担。同一个体内RBC群体的一个公认但知之甚少的特征是其表型异质性。在正常和疾病状态下的表型RBC变异的颗粒表征可能使我们能够识别红细胞疾病的遗传决定因素，并揭示其治疗的新治疗方法。以前，我们在红细胞中发现了不同的RNA转录物，这使我们能够剖析镰状红细胞的表型异质性和抗疟疾性。然而，这些分析未能捕获RBC亚群中发现的异质性。为了克服这一限制，我们进行了单细胞RNA-Seq以分析来自三名成年健康供体的RBC的转录异质性，这些供体已储存在血库条件下并在第1天和第15天进行测定。表达模式清楚地将RBC分成七个不同的簇，包括一个表达HBG 2的RBC簇和一小部分表达胎儿血红蛋白（HbF）的RBC，我们将其注释为F细胞。几乎所有的HBG 2表达细胞也表达HBB，表明来自HBG 2/HBB基因座的单个RBC中的双等位基因表达，并且我们基于典型基因表达将另一簇注释为网织红细胞。还基于NIX、ACVR 2B和HEMGN的富集表达注释了另外的RBC簇，其先前显示参与红细胞生成。最后，我们发现RBC的储存与ACVR 2B和F细胞簇的增加有关。总的来说，这些数据表明单个RBC RNA-Seq捕获和发现RBC群体的已知和意外异质性的能力。
Human red blood cells (RBCs), or erythrocytes, are the most abundant blood cells responsible for gas exchange. RBC diseases affect hundreds of millions of people and impose enormous financial and personal burdens. One well-recognized, but poorly understood feature of RBC populations within the same individual are their phenotypic heterogeneity. The granular characterization of phenotypic RBC variation in normative and disease states may allow us to identify the genetic determinants of red cell diseases and reveal novel therapeutic approaches for their treatment. Previously, we discovered diverse RNA transcripts in RBCs that has allowed us to dissect the phenotypic heterogeneity and malaria resistance of sickle red cells. However, these analyses failed to capture the heterogeneity found in RBC sub-populations. To overcome this limitation, we have performed single cell RNA-Seq to analyze the transcriptional heterogeneity of RBCs from three adult healthy donors which have been stored in the blood bank conditions and assayed at day 1 and day 15. The expression pattern clearly separated RBCs into seven distinct clusters that include one RBC cluster that expresses HBG2 and a small population of RBCs that express fetal hemoglobin (HbF) that we annotated as F cells. Almost all HBG2-expessing cells also express HBB, suggesting bi-allelic expression in single RBC from the HBG2/HBB loci, and we annotated another cluster as reticulocytes based on canonical gene expression. Additional RBC clusters were also annotated based on the enriched expression of NIX, ACVR2B and HEMGN, previously shown to be involved in erythropoiesis. Finally, we found the storage of RBC was associated with an increase in the ACVR2B and F-cell clusters. Collectively, these data indicate the power of single RBC RNA-Seq to capture and discover known and unexpected heterogeneity of RBC population.
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影响因子：
3.5
作者：
Rathjen, Tina;Nicol, Clare;Dalmay, Tamas
通讯作者：
Dalmay, Tamas
影响因子：
2.9
作者：
Kim-Shapiro DB;Lee J;Gladwin MT
通讯作者：
Gladwin MT
影响因子：
16.6
作者：
Mantel PY;Hjelmqvist D;Walch M;Kharoubi-Hess S;Nilsson S;Ravel D;Ribeiro M;Grüring C;Ma S;Padmanabhan P;Trachtenberg A;Ankarklev J;Brancucci NM;Huttenhower C;Duraisingh MT;Ghiran I;Kuo WP;Filgueira L;Martinelli R;Marti M
通讯作者：
Marti M
影响因子：
3.7
作者：
Doss, Jennifer F.;Jonassaint, Jude C.;Chi, Jen-Tsan
通讯作者：
Chi, Jen-Tsan
DOI：
10.1073/pnas.0708160104
发表时间：
2007-10-23
影响因子：
11.1
作者：
Bennett-Guerrero, Elliott;Veldman, Tim H.;McMahon, Timothy J.
通讯作者：
McMahon, Timothy J.