At the beginning of life, the sperm and the egg combine to produce a fertilized egg, and the cell begins to divide.
In order to open the "black box" of embryonic development, Du Zhuo's research group at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences (hereinafter referred to as the Institute of Genetics and Development) drew a protein map at the single-cell level, which is like a high-precision navigation map.
A molecular map to understand embryonic development
A molecular map to understand embryonic development The construction of living organisms begins with embryonic development, and its regulation is highly dynamic and complex
"How to establish a developmental schema, that is, how each cell produced by a fertilized egg obtains a specific fate and builds a complete morphological and functional tissues and organs, is the core issue of embryonic development
In the 1970s and 1980s, the pioneer of developmental biology, John Sulston, by mapping the developmental origins and lineage relationships of all the somatic cells of C.
However, the molecular characteristics of cells involved in development have not been fully elucidated, and the internal molecular dynamics regulation process still needs to be deepened
"An entry point is to clarify the gene expression and regulation of each cell at each moment
Using the protein fusion fluorescent reporter system and four-dimensional real-time imaging technology, Zhu Zhuo’s research group has drawn a protein map, which is like a GPS real-time navigation map, which contains hundreds of transcription factors in almost all cell lineages during the embryonic development of nematodes.
Dynamically reveal the "fate" of cells
Dynamically reveal the "fate" of cells In the process of embryonic development, how do cells follow different "destiny tracks", develop into different organs, or play different roles?
By focusing on the key genes for developmental regulation-transcription factors, Zhu Zhuo's research group has constructed hundreds of fluorescent reporter lines that can indicate the dynamic expression of proteins in the new study, integrating in vivo imaging, cell identification, real-time lineage tracking, and single-cell fluorescence quantitative analysis Analyzed the dynamic protein expression of transcription factors in each cell at the in situ, 4D, and single-cell level
The author uses a non-invasive method to accurately determine cell identity through imaging and cell tracking, and systematically integrates the single-cell expression levels of multiple proteins to achieve true protein dynamic expression analysis with single-cell annotation accuracy
"This is a very high-quality paper that describes the expression patterns of 266 transcription factor proteins
Using this map, the author first analyzed the molecular regulatory framework established by the cell fate scheme from multiple dimensions
"Each level of distinction involves multiple different transcription factors with similar expression parts, giving a high degree of stability to the regulatory process
In order to understand the developmental function of transcription factors, the study integrates single-cell expression similarity and transcription factor-target gene information based on experimental data, and constructs a spatio-temporal specific regulatory loop, covering the regulatory relationship between more than 8000 transcription factors in 161 developmental spatiotemporal modules , And based on this, revealed the new functions of classical regulatory genes and new developmental regulatory processes
For example, studies have found that in addition to the classic regulation of epidermal cell fate, the ELT-1/GATA3 gene also controls the fate of neural precursor cells of the same lineage, suggesting that the essence of ELT-1 function is to regulate both epidermal and neural fate at the lineage level
The study also revealed the key function of M03D4.
4/VEZF1 in the convergent differentiation of muscle subtype cells.
Different upstream regulatory signals of body wall and throat muscle cells converge in M03D4.
4, which is activated and functions in coordination with it.
Regulating muscle function genes thus mediates the convergent differentiation process of cells of the same type with different developmental origins located in different parts of the body
.
Therefore, the high-precision "expression-inspiring" research paradigm can efficiently analyze developmental regulation
.
In this regard, another reviewer pointed out that the author was able to identify the regulators of embryonic development because of the use of many advanced research methods.
methods for protein binding sites efficient and accurate screening and identification of genome-wide), the combination of functional experiments
.
He/she pointed out that the resulting single-cell protein dynamic expression profile "can be further used to derive new hypotheses that can be verified by experiments
.
"
Leading a new understanding of developmental regulation
Leading a new understanding of developmental regulation Not just drawing a "map", the researchers also hope to "follow the picture" to help simulate and analyze the dynamic relationship between cell regulation and cell fate
.
Based on the integration of molecular and cellular maps with high temporal and spatial precision, researchers have systematically explored the diversity and complexity of cell regulatory states
.
As a result, it was found that the regulatory state first showed a high degree of differentiation with the unfolding of the lineage.
Although the same tissue cells were subsequently converged, they still showed a high degree of state diversity depending on the lineage source
.
"Therefore, the developmental history of a cell has a non-negligible influence on the shaping of its final function, and the organization of the lineage determines the diversity of the state and function of the same cell
.
" said Zhao Zhiguang, the co-first author of the paper and a doctoral student
.
The study further found that the regulatory state of cells continued to change with development until the end of division, and its transition trajectory was highly non-directional, suggesting that Waddington's developmental landforms (the theory proposed by geneticist Conrad Hal Waddington, there are fork roads at different locations of development, leading to Different paths) meandering, the cell goes through multiple intermediate states, and reaches the end through a long “detour”
.
The author stated that this study provides complete, accurate and standardized reference information for the analysis of molecular regulation of embryonic development, for the study of "expression-inspired" gene development function, regulatory status-functional quantitative biological research, single cell-whole embryo- Lay the foundation for multi-dimensional systems biology research
.
"For'higher' model animals, single-cell analysis may be a new field, and nematode developmental biology has entered the single-cell era for more than 40 years
.
" Du Zhuo said, "Our research suggests that even if it consists of only a thousand cells The cognition of the dynamics, diversity and complexity of its developmental regulation has just begun
.
"
The new research is undoubtedly leading in this respect
.
As one of the reviewers said: “This study provides a very valuable resource and demonstrates its utility.
It is not only for embryo researchers, but also for people interested in the interaction of transcription factors in other biological process research.
Same
.
"
Du Zhuo’s research group Ma Xuehua, Zhao Zhiguang, and Xiao Long are the co-first authors of this paper.
Xu Weina, Kou Yahui, Wang Yangyang, and Zhang Yanping and Wu Gang from the Dong Mengqiu Laboratory of the Beijing Institute of Life Sciences participated in some of the work
.
This research was funded by the Strategic Leading Science and Technology Project of the Chinese Academy of Sciences (Category B), the National Natural Science Foundation of China and the State Key Laboratory of Molecular Developmental Biology
.
(Source: Feng Lifei, China Science News)
Related paper information:
https://doi.
org/10.
1038/s41592-021-01216-1
https://doi.
org/10.
1038/s41592-021-01216-1
Transcription factor single-cell protein expression dynamic map reveals the basic framework of molecular regulation for the establishment of developmental fate patterns Ma Xuehua et al.
This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only.
This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of
the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed
description of the concern or complaint, to
service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content
will be removed immediately.
