Reviewer response for version 1
The authors have developed an easy to follow workflow which goes beyond preparing single-cell data for analysis, showing how to use existing methods and packages to normalize, perform dimension reduction, construct cell lineages and perform differential testing along those lineages. 
The workflow seems like it will be useful, and I hope the authors can update the workflow as new frameworks come into play (e.g. SingleCellExperiment).
I have the following suggestions for improving the workflow:
It would be useful to put a link to the source code (or to the section where the link to the source code exists) near the top of the document.
I was confused a bit by "the first major bifurcation in the HBC lineage trajectory occurs prior to cell division". 
Can you be more specific about what you are referring to here by cell division, as without knowledge of the system, I'm not sure where the cell division you refer to should appear.
"within a single object": It may be good to explain what an "object" here is. 
You could, for example, refer to Figure 2 of the Bioconductor Nature Methods paper 1 .
Misspelling: "reasonnable"
On filtering for most variable genes, I understand this decision, and I also recommend it during workshops before making ordination plots. 
I know that students are not always certain why we care about variance (unsupervised). 
I like to mention that these are the genes where the "action" is. 
A side point, the log(x+1) is not variance stabilizing for RNA-seq counts in general. 
This filter can give higher priority to low count genes than to genes where there is interesting biological variability (though I do not doubt that the very high biological variance genes will be preserved). 
It might be useful to show a vsn::meanSdPlot() for the matrix log1p(assay(se))?
"correcting for batch effects": What are batch effects? 
(Of course, I know what they are, but a reader may not, and you could cite some of the single cell literature here.)
"Note that, in this case, the low-dimensional matrix W is not included in the computation of residuals to avoid the removal of the biological signal of interest.": I understood this sentence only on a second pass through. 
One problem is that you haven't defined W in the text yet (only in Figure 4). 
I would only reference the matrix W if you have defined it.
Figure 6: 
Can you change the figure width so that PC1 is not squished?
Is there a circularity to the recovery of published clusters in Figure 6? 
Was ZINB-WaVE used in Fletcher (2017)?
Can you say what the meaning of the color white is in Figure 8 (in the text or caption near this figure)?
Figure 15 refers back to Figure 2 but does not use the same color scheme for the known cell types, so the reader cannot verify if you've recovered the lineages from the publication. 
It would be good therefore to have a legend for these figures (Fig 15 and following) indicating which cell types the colors refer to (this information is in the unlabeled table above, but should be included as a legend here).
Can you briefly describe what a GAM is ahead of Figure 17?
Structure
Recap
Strength
Structure
Todo
Weakness
Todo
Todo
Todo
Weakness
Strength
Other
Other
Other
Other
Todo
Todo
Todo
Weakness
Weakness
Todo
Structure
Todo
Todo
Todo
Todo
Weakness
Todo
Todo