Meaning of “gene expression heterogeneity” of embryonic stem cells

Question

What does it mean if a gene has a heterogeneous expression? Does it describe the differences of patterns of expression of that particular gene in a population of cells that are identical? The papers I have found did not really elaborate on what it meant, and I do not know where else to find the definition.

In particular, I want to understand heterogeneity in the context of stem cells. In the paper by Angarica and Sol, 2016, it reads:

“Experimental studies at the single-cell level have revealed that embryonic stem cells (ESCs), and more generally pluripotent stem cells (PSCs), exhibit significant gene expression heterogeneity.”

“Single-cell studies have allowed gene clustering, depending on the levels of heterogeneity in the gene expression landscape in PSCs.”

Does it have more to do with the variation of its expression in the population?

“In mouse ESCs genes exist that are uniformly expressed in most cells and exhibiting a unimodal distribution (Oct4, Rest, Tcf3, Sal4); other genes exhibit bimodal expression and are expressed in some populations but not in others (Nanog, Rex1, Tet1, Esrrb), and yet another group of genes display sporadic expression (Neurod1, Klf4, Otx2, Pax6) and are undetected in most cells but highly expressed in some specific subpopulations.”

Reference:

1. Angarica and Sol, 2016, Modeling heterogeneity in the pluripotent state: A promising strategy for improving the efficiency and fidelity of stem cell differentiation.

Answer 1

Heterogeneity is a noun meaning:

the fact of consisting of parts or things that are very different from each other

In scientific use the context determines what is differing.

The context here is gene expression in individual embryonic stem cells (presumably single-cell RNASeq). Here the heterogeneity in expression would be for the genes

…(Neurod1, Klf4, Otx2, Pax6)

for which the expression is

…undetected in most cells but highly expressed in some specific subpopulations.

The conclusion is that although the embryonic stem cells may appear to be a homogeneous population (all alike) and do show similarities in many genes that they express, they must, in fact be a mixture of two (or more) types. (This makes the generally accepted assumption that the basis for distinguishing cells is the genes they express and the proteins they make.)

Thus the idea, expressed in the question, that the cells are identical is incorrect. I know little about stem cell differentiation, but I would assume the implication is that the subpopulation will differentiate on a different path to the rest of the population, or that it has already started to differentiate, or something of the sort (which I imagine is discussed in the paper).