Cellular Barcoding Links B-1a B Cell Potential to a Fetal Hematopoietic Stem Cell State at the Single-Cell Level.

Kristiansen TA, Jaensson Gyllenbäck E, Zriwil A, Björklund T, Daniel JA, Sitnicka E, Soneji S, Bryder D, Yuan J

Immunity 45 (2) 346-357 [2016-08-16; online 2016-08-18]

Hematopoietic stem cells (HSCs) undergo a functional switch in neonatal mice hallmarked by a decrease in self-renewing divisions and entry into quiescence. Here, we investigated whether the developmental attenuation of B-1a cell output is a consequence of a shift in stem cell state during ontogeny. Using cellular barcoding for in vivo single-cell fate analyses, we found that fetal liver definitive HSCs gave rise to both B-1a and B-2 cells. Whereas B-1a potential diminished in all HSCs with time, B-2 output was maintained. B-1a and B-2 plasticity could be reinitiated in a subset of adult HSCs by ectopic expression of the RNA binding protein LIN28B, a key regulator of fetal hematopoiesis, and this coincided with the clonal reversal to fetal-like elevated self-renewal and repopulation potential. These results anchor the attenuation of B-1a cell output to fetal HSC behavior and demonstrate that the developmental decline in regenerative potential represents a reversible HSC state.

Bioinformatics Support for Computational Resources [Service]

NGI Uppsala (Uppsala Genome Center) [Service]

National Genomics Infrastructure [Service]

PubMed 27533015

DOI 10.1016/j.immuni.2016.07.014

Crossref 10.1016/j.immuni.2016.07.014

pii: S1074-7613(16)30287-4