Single-cell spatial reconstruction reveals global division of labour in the mammalian liver

肝小叶 生物 转录组 基因 计算生物学 遗传学 基因表达 内分泌学
作者
Keren Bahar Halpern,Rom Shenhav,Orit Matcovitch-Natan,Beáta Tóth,Doron Lemze,Matan Golan,Efi E. Massasa,Shaked Baydatch,Shanie Landen,Andreas E. Moor,Alexander Brandis,Amir Giladi,Avigail Stokar-Avihail,Eyal David,Ido Amit,Shalev Itzkovitz
出处
期刊:Nature [Nature Portfolio]
卷期号:542 (7641): 352-356 被引量:924
标识
DOI:10.1038/nature21065
摘要

Single-molecule fluorescence in situ hybridization is performed to identify several landmark genes in the liver and their level of expression in single-cell RNA sequencing is used to spatially reconstruct the zonation of all liver genes. A few important liver genes are differentially expressed in a radial fashion from the central vein outward, but the extent of such spatial division, or zonation, has remained unknown. Shalev Itzkovitz, Ido Amit and colleagues performed single-molecule fluorescence in situ hybridization against several landmark genes, and used their level of expression to spatially reconstruct the zonation of all liver genes. They find that around half of the genes in the liver are zonated, and surprisingly also find that several genes peak in the middle of the liver lobules. The succession of gene expression profiles matches the position of proteins in the bile-acid biosynthetic cascade. The mammalian liver consists of hexagon-shaped lobules that are radially polarized by blood flow and morphogens1,2,3,4. Key liver genes have been shown to be differentially expressed along the lobule axis, a phenomenon termed zonation5,6, but a detailed genome-wide reconstruction of this spatial division of labour has not been achieved. Here we measure the entire transcriptome of thousands of mouse liver cells and infer their lobule coordinates on the basis of a panel of zonated landmark genes, characterized with single-molecule fluorescence in situ hybridization7. Using this approach, we obtain the zonation profiles of all liver genes with high spatial resolution. We find that around 50% of liver genes are significantly zonated and uncover abundant non-monotonic profiles that peak at the mid-lobule layers. These include a spatial order of bile acid biosynthesis enzymes that matches their position in the enzymatic cascade. Our approach can facilitate the reconstruction of similar spatial genomic blueprints for other mammalian organs.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
QOP应助hhhhhhhh采纳,获得10
1秒前
沉静高山发布了新的文献求助10
2秒前
LUO完成签到,获得积分10
2秒前
黑骑士完成签到,获得积分10
2秒前
Owen应助澳澳采纳,获得10
3秒前
星禾吾完成签到,获得积分10
4秒前
彭a完成签到,获得积分10
5秒前
怕黑丹珍完成签到,获得积分10
5秒前
7秒前
8秒前
香蕉觅云应助hui采纳,获得10
9秒前
外向豁完成签到,获得积分10
11秒前
11秒前
13秒前
小二郎应助花猹猹采纳,获得10
13秒前
Ingram发布了新的文献求助50
13秒前
14秒前
劲秉应助kcmat采纳,获得10
14秒前
研友_89jWGL发布了新的文献求助10
16秒前
知行合一发布了新的文献求助10
16秒前
科研通AI5应助肉团子采纳,获得30
17秒前
Nothing1024完成签到,获得积分10
17秒前
WQY发布了新的文献求助10
18秒前
科研通AI2S应助冷傲天川采纳,获得10
18秒前
SICHEN应助冷傲天川采纳,获得10
18秒前
碧蓝的初南完成签到,获得积分10
21秒前
畅快的明杰完成签到,获得积分10
23秒前
24秒前
isabella完成签到,获得积分20
25秒前
清图完成签到,获得积分10
26秒前
科科科科呃完成签到,获得积分10
26秒前
Hiraeth完成签到 ,获得积分10
26秒前
26秒前
Nothing1024发布了新的文献求助10
28秒前
天真怜晴完成签到,获得积分10
30秒前
科研通AI5应助aaaaa采纳,获得10
30秒前
伍思光完成签到,获得积分20
30秒前
酷炫毛豆完成签到,获得积分10
30秒前
31秒前
烟花应助小叙采纳,获得10
32秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2700
Ophthalmic Equipment Market 1500
Neuromuscular and Electrodiagnostic Medicine Board Review 1000
こんなに痛いのにどうして「なんでもない」と医者にいわれてしまうのでしょうか 510
いちばんやさしい生化学 500
The First Nuclear Era: The Life and Times of a Technological Fixer 500
Unusual formation of 4-diazo-3-nitriminopyrazoles upon acid nitration of pyrazolo[3,4-d][1,2,3]triazoles 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3672767
求助须知:如何正确求助?哪些是违规求助? 3228872
关于积分的说明 9782477
捐赠科研通 2939308
什么是DOI,文献DOI怎么找? 1610825
邀请新用户注册赠送积分活动 760740
科研通“疑难数据库(出版商)”最低求助积分说明 736199