Common and distinct transcriptional signatures of mammalian embryonic lethality

被引：13

作者：

Collins, John E. ^{[1
]}

White, Richard J. ^{[1
,2
]}

Staudt, Nicole ^{[1
]}

Sealy, Ian M. ^{[1
,2
]}

Packham, Ian ^{[1
]}

Wali, Neha ^{[1
]}

Tudor, Catherine ^{[1
]}

Mazzeo, Cecilia ^{[1
]}

Green, Angela ^{[1
]}

Siragher, Emma ^{[1
]}

Ryder, Edward ^{[1
]}

White, Jacqueline K. ^{[1
,9
]}

Papatheodoru, Irene ^{[3
]}

Tang, Amy ^{[3
]}

Fullgrabe, Anja ^{[3
]}

Bills, Konstantinos ^{[3
]}

Geyer, Stefan H. ^{[4
]}

Weninger, Wolfgang J. ^{[4
]}

Galli, Antonella ^{[1
]}

Hemberger, Myriam ^{[5
,6
,10
,11
]}

Stemple, Derek L. ^{[1
,12
]}

Robertson, Elizabeth ^{[7
]}

Smith, James C. ^{[8
]}

Mohun, Timothy ^{[8
]}

Adams, David J. ^{[1
]}

Busch-Nentwich, Elisabeth M. ^{[1
,2
]}

机构：

[1] Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England

[2] Univ Cambridge, CITIId, Jeffrey Cheah Biomed Ctr, Puddicombe Way, Cambridge CB2 0AW, England

[3] European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England

[4] Med Univ Vienna, Div Anat, MIC, Waehringerstr 13, A-1090 Vienna, Austria

[5] Babraham Inst, Babraham Res Campus, Cambridge CB22 3AT, England

[6] Univ Cambridge, Ctr Trophoblast Res, Downing St, Cambridge CB2 3EG, England

[7] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[8] Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England

[9] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA

[10] Univ Calgary, Cumming Sch Med, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada

[11] Univ Calgary, Cumming Sch Med, Dept Med Genet, Calgary, AB T2N 4N1, Canada

[12] Camena Biosci, Chesterford Res Pk, Cambridge CB10 1XL, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

GENE-EXPRESSION DATA; TRANSPOSABLE ELEMENTS; MOUSE; GENERATION; ALIGNMENT; MUTATION; SHH; DEFICIENCY; MECHANISMS; INTERACTS;

D O I：

10.1038/s41467-019-10642-x

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Deciphering the Mechanisms of Developmental Disorders programme has analysed the morphological and molecular phenotypes of embryonic and perinatal lethal mouse mutant lines in order to investigate the causes of embryonic lethality. Here we show that individual whole-embryo RNA-seq of 73 mouse mutant lines (>1000 transcriptomes) identifies transcriptional events underlying embryonic lethality and associates previously uncharacterised genes with specific pathways and tissues. For example, our data suggest that Hmgxb3 is involved in DNA-damage repair and cell-cycle regulation. Further, we separate embryonic delay signatures from mutant line-specific transcriptional changes by developing a baseline mRNA expression catalogue of wild-type mice during early embryogenesis (4-36 somites). Analysis of transcription outside coding sequence identifies deregulation of repetitive elements in Morc2a mutants and a gene involved in gene-specific splicing. Collectively, this work provides a large scale resource to further our understanding of early embryonic developmental disorders.

引用

页数：16

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