Figure 1: System overview.

(a) Lentiviral constructs used to generate stable cells lines. (b) General timeline for experiments, media conditions and cell extractions for exome microarray analysis. Y, rock-inhibitor; Dox, doxycycline; PP-Med., pluripotency supporting medium. Basal medium: medium without additional growth factors or serum. Filled arrows: RNA isolation and microarray analysis from total cells. Open arrows: RNA isolation and microarray analysis from enriched cells (CXCR4, CD34: enrichment using MACS beads; man. extr., manual extraction of early neuronal cell clusters). (c) Process overview (left) and a model of cell types generated during experiment (right). hiPSC containing an inducible GATA6 transgene are seeded in a monolayer. Transgene expression is then triggered with a small inducer molecule (Dox) causing the cells to co-differentiate. Starting with an undifferentiated monolayer of hiPSCs, we obtain complex tissue after 15 days. LBLT, liver bud-like tissue; NPL, neuronal progenitor-like; HPN, haematopoietic niche. HPN includes all cellular components developed within the system, which directly or indirectly support emergence of haematopoietic-like processes. For more information refer to the text. ME, mesendoderm, PP: pluripotent cells (expressing pluripotency markers, not induced to mesendoderm), En, endoderm; Me, mesoderm; Ec, ectoderm; HpEn, hepatic endoderm; EP, endothelial progenitors; MP, mesenchymal progenitors; Ec, ectoderm; NEc, neurectoderm; HpLC, hepatocyte-like cells; ChLC, cholangiocyte-like cells; EnLC, endothelial-like cells; HE, haemangioblast-like cells; ErLC, erythrocyte-like cells; HmLC, haematopoietic progenitor-like cells; StLC, stellate-like cells; MsLC, mesenchyme/pericyte-like cells; NEp, neuronal progenitors.