PMID- 28001340 OWN - NLM STAT- MEDLINE DCOM- 20171113 LR - 20181113 IS - 1939-005X (Electronic) IS - 1939-5094 (Print) IS - 1939-005X (Linking) VI - 9 IP - 2 DP - 2017 Mar TI - Quantitative approaches for investigating the spatial context of gene expression. LID - 10.1002/wsbm.1369 [doi] LID - e1369 AB - The spatial information associated with gene expression is important for elucidating the context-dependent transcriptional regulation during development. Recently, high-resolution sampling approaches, such as RNA tomography or single-cell RNA-seq combined with fluorescence in situ hybridization (FISH), have provided indirect ways to view global gene expression patterns in three dimensions. Now in situ sequencing technologies, such as fluorescent in situ sequencing (FISSEQ), are attempting to visualize the genetic signature directly in microscope images. This article will examine the basic principle of modern in situ and single-cell genetic methods, hurdles in quantifying intrinsic and extrinsic forces that influence cell decision-making, and technological requirements for making a visual map of gene regulation, form, and function. Successfully addressing these challenges will be essential for investigating the functional evolution of regulatory sequences during growth, development, and cancer progression. WIREs Syst Biol Med 2017, 9:e1369. doi: 10.1002/wsbm.1369 For further resources related to this article, please visit the WIREs website. CI - (c) 2016 The Authors. WIREs Systems Biology and Medicine published by Wiley Periodicals, Inc. FAU - Lee, Je H AU - Lee JH AUID- ORCID: 0000-0001-6947-7446 AD - Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA. LA - eng GR - P30 CA045508/CA/NCI NIH HHS/United States GR - R35 GM119772/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Review DEP - 20161221 PL - United States TA - Wiley Interdiscip Rev Syst Biol Med JT - Wiley interdisciplinary reviews. Systems biology and medicine JID - 101516550 SB - IM MH - Animals MH - Cellular Microenvironment MH - *Gene Expression MH - High-Throughput Nucleotide Sequencing/*methods MH - Humans MH - Imaging, Three-Dimensional MH - In Situ Hybridization, Fluorescence/*methods MH - Neoplasms/genetics/metabolism/pathology MH - Nucleic Acid Amplification Techniques MH - Sequence Analysis, RNA MH - Single-Cell Analysis PMC - PMC5315614 MID - NIHMS827511 EDAT- 2016/12/22 06:00 MHDA- 2017/11/14 06:00 PMCR- 2017/03/02 CRDT- 2016/12/22 06:00 PHST- 2016/08/09 00:00 [received] PHST- 2016/10/19 00:00 [revised] PHST- 2016/10/25 00:00 [accepted] PHST- 2016/12/22 06:00 [pubmed] PHST- 2017/11/14 06:00 [medline] PHST- 2016/12/22 06:00 [entrez] PHST- 2017/03/02 00:00 [pmc-release] AID - WSBM1369 [pii] AID - 10.1002/wsbm.1369 [doi] PST - ppublish SO - Wiley Interdiscip Rev Syst Biol Med. 2017 Mar;9(2):e1369. doi: 10.1002/wsbm.1369. Epub 2016 Dec 21.