PT  - JOURNAL ARTICLE
AU  - P. J. Fabre
AU  - M. Leleu
AU  - B. Mascrez
AU  - Q. Lo Giudice
AU  - J. Cobb
AU  - D. Duboule
TI  - Single-cell mRNA profiling reveals heterogeneous combinatorial expression of <em>Hoxd</em> genes during limb development
AID  - 10.1101/327619
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 327619
4099  - http://biorxiv.org/content/early/2018/05/22/327619.2.short
4100  - http://biorxiv.org/content/early/2018/05/22/327619.2.full
AB  - A global analysis of gene expression during development reveals specific transcription patterns associated with the emergence of various cell types, tissues and organs. These heterogeneous patterns are instrumental to ensure the proper formation of the different parts of our body, as shown by the phenotypic effects generated by functional genetic approaches. However, variations at the cellular level can be observed within each structure or organ. In the developing mammalian limbs, expression of Hoxd genes is differentially controlled in space and time in cells that will pattern the digits and the arms. Here we analyze single-cell transcriptomes of limb bud cells and show that Hox genes are expressed in specific combinations that match particular cell types. In the presumptive digits, we find that the expression of Hoxd gene is unbalanced, despite their common genomic proximity to known global enhancers, often expressing only a subset of the five genes transcribed in these cells. We also report that combinatorial expression follows a pseudo-time sequence, suggesting that a progression in combinatorial expression may be associated with cellular diversity in developing digits.Collinear expression of Hox genes is only weaved at the tissue scaleEnhancer-sharing to specific target genes is reduced at the single-cell levelHoxd gene combinatorial expression is linked to distinct transcriptional signaturesIn presumptive digits, Hoxd combinations follow a pseudotime trajectory