Abstract
Single-cell sequencing technologies enhance our understanding of cellular dynamics throughout pregnancy. We outlined the workflow of single-cell sequencing techniques and reviewed single-cell studies in maternal and child health. We conducted a literature review of single cell studies on maternal and child health using PubMed. We summarized the findings from 16 single-cell atlases of the human and mammalian placenta across gestational stages and 31 single-cell studies on maternal exposures and complications including infection, obesity, diet, gestational diabetes, pre-eclampsia, environmental exposure and preterm birth. Single-cell studies provides insights on novel cell types in placenta and cell type-specific marks associated with maternal exposures and complications.
Plain language summary
Single-cell sequencing technologies offer new biological insights on pregnancy at the cellular level. We reviewed these technologies and their applications in maternal and child health studies, including 16 placenta cell databases and 31 studies on health challenges during pregnancy such as COVID infection. New cell types and biological pathways among specific groups of cells were found.
TWEETABLE ABSTRACT
Single-cell sequencing offers new insights on maternal and child health. We reviewed 16 placental cell atlases and 31 single-cell studies on novel biological pathways on pregnancy complications.
Advancement in single-cell studies
Single-cell studies in maternal and child health has progressed from analyzing 87 cells to tens of thousands. The scope expanded from creating cell atlases of placenta tissues during normal pregnancy to understanding mechanisms of pregnancy complications.
Single-cell atlases on placenta
Single-cell atlases of placental villi and decidua provide cellular references for fetal and maternal cell types, and their transcriptomic and epigenomic dynamics across various stages of pregnancy in humans and mammalians.
Single-cell studies on maternal exposure & complications
Single-cell studies reveal new cell subpopulations, cellular compositional changes and cell type-specific transcriptomic and epigenomic alterations due to maternal exposures and complications. These findings shed new insights on how maternal exposures and complications - including infection, obesity, diet, gestational diabetes, pre-eclampsia, chemical exposure and preterm birth – affects maternal and child health.
Future directions
Future research in single-cell studies on maternal and child health should focus on increasing sample sizes and diversity to enhance replication and reliability. The development of novel methods for data integration is crucial to address the analytical challenges posed by the variability and noise in larger datasets. There is also a pressing need to expand the scope of research beyond transcriptomics to include single-cell epigenomics to provide deeper insights into the regulatory mechanisms during pregnancy. Additionally, establishing a comprehensive cell atlas of normal placenta tissues, particularly at delivery and investigating the longitudinal effects of maternal environmental exposures across various gestational stages in animal models are vital.
Author contribution
C Shu conducted the literature review and wrote the manuscript. K Street edited the sections on overview of single-cell sequencing technology and future directions. C Breton, T Bastain and M Wilson edited the sections on introduction, single-cell atlases in placenta during normal pregnancy, single-cell transcriptomics and epigenomics studies on maternal exposure and complications and future directions.
Financial disclosure
This work is supported by Southern California Environmental Health Sciences Center pilot grant from NIH/NIEHS, grant number P30ES007048 (Rob McConnell).
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Competing interest disclosure
The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.