scRNA-seq的表达矩阵待解决的发育生物学问题

不同细胞类型有绝对界限吗？决定不同细胞类型的基因有定数吗？或者说是基因集？细胞分化过程的时空动态变化细节？

五大问题：

• (1) Are there distinct clusters of cells within the general cell population (corresponding to either a variety of differentiation stages or to various, fully-differentiated, celltypes)?

• (2) Which genes characterize each cell population?

• (3) Which gene modules regulate differentiation?

• (4) How do cells progress through the differentiation process?

• (5) How is the differentiation process spatially reflected in the relevant tissue?

解决方案

• (1) Finding cell clusters can be achieved by applying dimensionality reduction techniques or clustering algorithms

• (2) The biological roles of the identified clusters can then be evaluated based on genes that differentially expressed (DE) between clusters, using available methods to infer differential expression

• (3) Measuring gene co-occurrence or gene-gene correlations across single-cells can be used to build coexpression networks that can yield insights into important gene modules and gene regulation involved in differentiation.

• (4) Although single-cell data of a differentiation path is a static snapshot, differentiation is a dynamic and continuous process, encompassing a continuous range of cell-states along this process.

• (5) This can be achieved computationally by mapping single-cells against a spatial reference,allowing the spatial visualization of cell subpopulations, markers and gene modules identified in previous stages.

In summary, the above-mentioned approaches allow the identification of subsets of cells, the genes that give rise to the differences between these subsets, how these differences are established and their underlying regulatory networks.