Single-cell chromatin accessibility landscape of human umbilical cord blood in trisomy 18 syndrome

Abstract Background Trisomy 18 syndrome (Edwards syndrome, ES) is a type of aneuploidy caused by the presence of an extra chromosome 18. Aneuploidy is the leading cause of early pregnancy loss, intellectual disability, and multiple congenital anomalies. The research of trisomy 18 is progressing slow...

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Main Authors: Xiaofen Qiu, Haiyan Yu, Hongwei Wu, Zhiyang Hu, Jun Zhou, Hua Lin, Wen Xue, Wanxia Cai, Jiejing Chen, Qiang Yan, Weier Dai, Ming Yang, Donge Tang, Yong Dai
Format: Article
Language:English
Published: BMC 2021-06-01
Series:Human Genomics
Subjects:
Online Access:https://doi.org/10.1186/s40246-021-00338-z
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language English
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author Xiaofen Qiu
Haiyan Yu
Hongwei Wu
Zhiyang Hu
Jun Zhou
Hua Lin
Wen Xue
Wanxia Cai
Jiejing Chen
Qiang Yan
Weier Dai
Ming Yang
Donge Tang
Yong Dai
spellingShingle Xiaofen Qiu
Haiyan Yu
Hongwei Wu
Zhiyang Hu
Jun Zhou
Hua Lin
Wen Xue
Wanxia Cai
Jiejing Chen
Qiang Yan
Weier Dai
Ming Yang
Donge Tang
Yong Dai
Single-cell chromatin accessibility landscape of human umbilical cord blood in trisomy 18 syndrome
Human Genomics
Trisomy 18 syndrome
single-cell sequencing
Transcription factors
Aneuploidy
Developmental regulation
author_facet Xiaofen Qiu
Haiyan Yu
Hongwei Wu
Zhiyang Hu
Jun Zhou
Hua Lin
Wen Xue
Wanxia Cai
Jiejing Chen
Qiang Yan
Weier Dai
Ming Yang
Donge Tang
Yong Dai
author_sort Xiaofen Qiu
title Single-cell chromatin accessibility landscape of human umbilical cord blood in trisomy 18 syndrome
title_short Single-cell chromatin accessibility landscape of human umbilical cord blood in trisomy 18 syndrome
title_full Single-cell chromatin accessibility landscape of human umbilical cord blood in trisomy 18 syndrome
title_fullStr Single-cell chromatin accessibility landscape of human umbilical cord blood in trisomy 18 syndrome
title_full_unstemmed Single-cell chromatin accessibility landscape of human umbilical cord blood in trisomy 18 syndrome
title_sort single-cell chromatin accessibility landscape of human umbilical cord blood in trisomy 18 syndrome
publisher BMC
series Human Genomics
issn 1479-7364
publishDate 2021-06-01
description Abstract Background Trisomy 18 syndrome (Edwards syndrome, ES) is a type of aneuploidy caused by the presence of an extra chromosome 18. Aneuploidy is the leading cause of early pregnancy loss, intellectual disability, and multiple congenital anomalies. The research of trisomy 18 is progressing slowly, and the molecular characteristics of the disease mechanism and phenotype are still largely unclear. Results In this study, we used the commercial Chromium platform (10× Genomics) to perform sc-ATAC-seq to measure chromatin accessibility in 11,611 single umbilical cord blood cells derived from one trisomy 18 syndrome patient and one healthy donor. We obtained 13 distinct major clusters of cells and identified them as 6 human umbilical cord blood mononuclear cell types using analysis tool. Compared with the NC group, the ES group had a lower ratio of T cells to NK cells, the ratio of monocytes/DC cell population did not change significantly, and the ratio of B cell nuclear progenitor and megakaryocyte erythroid cells was higher. The differential genes of ME-0 are enriched in Human T cell leukemia virus 1 infection pathway, and the differential peak genes of ME-1 are enriched in apopotosis pathway. We found that CCNB2 and MCM3 may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin. Conclusions We have identified 6 cell populations in cord blood. Disorder in megakaryocyte erythroid cells implicates trisomy 18 in perturbing fetal hematopoiesis. We identified a pathway in which the master differential regulatory pathway in the ME-0 cell population involves human T cell leukemia virus 1 infection, a pathway that is dysregulated in patients with trisomy 18 and which may increase the risk of leukemia in patients with trisomy 18. CCNB2 and MCM3 in progenitor may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin, may be related to chromosomal abnormalities in trisomy 18.
topic Trisomy 18 syndrome
single-cell sequencing
Transcription factors
Aneuploidy
Developmental regulation
url https://doi.org/10.1186/s40246-021-00338-z
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spelling doaj-54af4f56b20b4021aad75af73dfeaa722021-07-04T11:18:56ZengBMCHuman Genomics1479-73642021-06-0115111310.1186/s40246-021-00338-zSingle-cell chromatin accessibility landscape of human umbilical cord blood in trisomy 18 syndromeXiaofen Qiu0Haiyan Yu1Hongwei Wu2Zhiyang Hu3Jun Zhou4Hua Lin5Wen Xue6Wanxia Cai7Jiejing Chen8Qiang Yan9Weier Dai10Ming Yang11Donge Tang12Yong Dai13Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s HospitalDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s HospitalDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s HospitalDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s HospitalDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s HospitalGuangxi Key Laboratory of Metabolic Diseases Research, Department of Clinical Laboratory of GuilinGuangxi Key Laboratory of Metabolic Diseases Research, Department of Clinical Laboratory of GuilinDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s HospitalGuangxi Key Laboratory of Metabolic Diseases Research, Department of Clinical Laboratory of GuilinGuangxi Key Laboratory of Metabolic Diseases Research, Department of Clinical Laboratory of GuilinCollege of Natural Science, University of Texas at AustinGuangxi Key Laboratory of Metabolic Diseases Research, Department of Clinical Laboratory of GuilinDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s HospitalDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s HospitalAbstract Background Trisomy 18 syndrome (Edwards syndrome, ES) is a type of aneuploidy caused by the presence of an extra chromosome 18. Aneuploidy is the leading cause of early pregnancy loss, intellectual disability, and multiple congenital anomalies. The research of trisomy 18 is progressing slowly, and the molecular characteristics of the disease mechanism and phenotype are still largely unclear. Results In this study, we used the commercial Chromium platform (10× Genomics) to perform sc-ATAC-seq to measure chromatin accessibility in 11,611 single umbilical cord blood cells derived from one trisomy 18 syndrome patient and one healthy donor. We obtained 13 distinct major clusters of cells and identified them as 6 human umbilical cord blood mononuclear cell types using analysis tool. Compared with the NC group, the ES group had a lower ratio of T cells to NK cells, the ratio of monocytes/DC cell population did not change significantly, and the ratio of B cell nuclear progenitor and megakaryocyte erythroid cells was higher. The differential genes of ME-0 are enriched in Human T cell leukemia virus 1 infection pathway, and the differential peak genes of ME-1 are enriched in apopotosis pathway. We found that CCNB2 and MCM3 may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin. Conclusions We have identified 6 cell populations in cord blood. Disorder in megakaryocyte erythroid cells implicates trisomy 18 in perturbing fetal hematopoiesis. We identified a pathway in which the master differential regulatory pathway in the ME-0 cell population involves human T cell leukemia virus 1 infection, a pathway that is dysregulated in patients with trisomy 18 and which may increase the risk of leukemia in patients with trisomy 18. CCNB2 and MCM3 in progenitor may be vital to the development of trisomy 18. CCNB2 and MCM3, which have been reported to be essential components of the cell cycle and chromatin, may be related to chromosomal abnormalities in trisomy 18.https://doi.org/10.1186/s40246-021-00338-zTrisomy 18 syndromesingle-cell sequencingTranscription factorsAneuploidyDevelopmental regulation