Single cell transcriptome analysis of human fetal pancreas.

Organ development is the process in which the mesoderm, endoderm and ectoderm develop into distinct cell types in highly ordered, discrete organs. Although model organisms have been hugely helpful to delineate the specific cell state transformations involved in organogenesis, the considerable differences in time-scale and physiology between human and such model organism can make direct comparisons difficult. Here, we analyze 1982 single cells from all cell lineages in the developing human pancreas, across a wide range of gestational stages (w 12 -22). We find that differentiation of endocrine progenitors into differentiated alpha and delta cells constitute branches in a “default” differentiation path into beta cells, a finding that is corroborated by in vivo reprogramming of alpha cells into beta cell in a mouse model. Further, we find several mesenchymal sub-cell types, the characteristic genes of which suggest specific roles in organ development including rapid cell growth, extracellular matrix reorganization and vascularization. Thus, our data suggests that to understand organ development, we have to chart the supporting mesenchymal cell types, some of which might only exist during organ development. Overall design: Examination of single cells from primary human pancreas tissue