Temporal specification of blood progenitors from mouse embryonic stem cells and induced pluripotent stem cells.
The efficient and reproducible generation of differentiated progenitors from pluripotent stem cells requires the recapitulation of appropriate developmental stages and pathways. Here, we have used the combination of activin A, BMP4 and VEGF under serum-free conditions to induce hematopoietic differentiation from both embryonic and induced pluripotent stem cells, with the aim of modeling the primary sites of embryonic hematopoiesis. We identified two distinct Flk1-positive hematopoietic populations that can be isolated based on temporal patterns of emergence. The earliest arising population displays characteristics of yolk sac hematopoiesis, whereas a late developing Flk1-positive population appears to reflect the para-aortic splanchnopleura hematopoietic program, as it has reduced primitive erythroid capacity and substantially enhanced myeloid and lymphoid potential compared with the earlier wave. These differences between the two populations are accompanied by differences in the expression of Sox17 and Hoxb4, as well as in the cell surface markers AA4.1 and CD41. Together, these findings support the interpretation that the two populations are representative of the early sites of mammalian hematopoiesis.
Irion
Stefan
S
McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON, Canada.
Clarke
Raedun L
RL
Luche
Hervé
H
Kim
Injune
I
Morrison
Sean J
SJ
Fehling
Hans-Joerg
HJ
Keller
Gordon M
GM
D028341:Activins / Q000008:administration & dosage; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D024002:HMGB Proteins / Q000235:genetics / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D038041:Lymphopoiesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011951:Receptors, Complement / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D024002:HMGB Proteins; D018398:Homeodomain Proteins; C513262:Hoxb4 protein, mouse; D008562:Membrane Glycoproteins; D040201:Platelet Membrane Glycoprotein IIb; D011951:Receptors, Complement; D011994:Recombinant Proteins; D055760:SOXF Transcription Factors; C511606:Sox17 protein, mouse; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C422405:activin A; C032402:complement 1q receptor; D028341:Activins; D040301:Vascular Endothelial Growth Factor Receptor-2