TY - UNPB
T1 - Single cell transcriptome analysis reveals markers of naïve and lineage-primed hematopoietic progenitors derived from human pluripotent stem cells
AU - Fidanza, Antonella
AU - Romanò, Nicola
AU - Ramachandran, Prakash
AU - Tamagno, Sara
AU - Lopez Yrigoyen, Martha
AU - Taylor, Helen
AU - Easterbrook, Jennifer
AU - Henderson, Beth
AU - Axton, Richard
AU - Henderson, Neil Cowan
AU - Medvinsky, Alexander
AU - Ottersbach, Katrin
AU - Forrester, Lesley M.
PY - 2019/4/11
Y1 - 2019/4/11
N2 - During embryogenesis the hematopoietic system develops through distinct waves that generate progenitors with increasing lineage potential, ultimately producing haematopoietic stem cells (HSCs). In vitro differentiation of human pluripotent stem cells (hPSCs) follows the early steps of haematopoietic development but the production of HSCs has proven more challenging. To study the dynamics and heterogeneity of hematopoietic progenitor cells generated in vitro from hPSCs, we performed RNA sequencing of over 10000 CD235a-CD43+single cells. We identified the transcriptome of naïve progenitors and those primed toward erythroid, megakaryocyte and leukocyte lineages, and revealed their markers by clustering, trajectory analyses and functional assays. CD44 marks naïve clonogenic progenitors that express the transcription factor, LMO4 and can be expanded upon BMP4 stimulation. Naïve progenitors give rise to primed CD326+erythroid, ICAM2+CD9+megakaryocyte, and monocyte, neutrophil and eosinophil progenitors. We have generated an online dataset of human hematopoietic progenitors and their transcriptional remodelling upon lineage priming.
AB - During embryogenesis the hematopoietic system develops through distinct waves that generate progenitors with increasing lineage potential, ultimately producing haematopoietic stem cells (HSCs). In vitro differentiation of human pluripotent stem cells (hPSCs) follows the early steps of haematopoietic development but the production of HSCs has proven more challenging. To study the dynamics and heterogeneity of hematopoietic progenitor cells generated in vitro from hPSCs, we performed RNA sequencing of over 10000 CD235a-CD43+single cells. We identified the transcriptome of naïve progenitors and those primed toward erythroid, megakaryocyte and leukocyte lineages, and revealed their markers by clustering, trajectory analyses and functional assays. CD44 marks naïve clonogenic progenitors that express the transcription factor, LMO4 and can be expanded upon BMP4 stimulation. Naïve progenitors give rise to primed CD326+erythroid, ICAM2+CD9+megakaryocyte, and monocyte, neutrophil and eosinophil progenitors. We have generated an online dataset of human hematopoietic progenitors and their transcriptional remodelling upon lineage priming.
U2 - 10.1101/602565
DO - 10.1101/602565
M3 - Preprint
BT - Single cell transcriptome analysis reveals markers of naïve and lineage-primed hematopoietic progenitors derived from human pluripotent stem cells
PB - bioRxiv
ER -