PMID- 29276152 OWN - NLM STAT- MEDLINE DCOM- 20181226 LR - 20210109 IS - 2213-6711 (Electronic) IS - 2213-6711 (Linking) VI - 10 IP - 1 DP - 2018 Jan 9 TI - In Vitro Differentiation of Gata2 and Ly6a Reporter Embryonic Stem Cells Corresponds to In Vivo Waves of Hematopoietic Cell Generation. PG - 151-165 LID - S2213-6711(17)30526-X [pii] LID - 10.1016/j.stemcr.2017.11.018 [doi] AB - In vivo hematopoietic generation occurs in waves of primitive and definitive cell emergence. Differentiation cultures of pluripotent embryonic stem cells (ESCs) offer an accessible source of hematopoietic cells for blood-related research and therapeutic strategies. However, despite many approaches, it remains a goal to robustly generate hematopoietic progenitor and stem cells (HP/SCs) in vitro from ESCs. This is partly due to the inability to efficiently promote, enrich, and/or molecularly direct hematopoietic emergence. Here, we use Gata2Venus (G2V) and Ly6a(SCA1)GFP (LG) reporter ESCs, derived from well-characterized mouse models of HP/SC emergence, to show that during in vitro differentiation they report emergent waves of primitive hematopoietic progenitor cells (HPCs), definitive HPCs, and B-lymphoid cell potential. These results, facilitated by enrichment of single and double reporter cells with HPC properties, demonstrate that in vitro ESC differentiation approximates the waves of hematopoietic cell generation found in vivo, thus raising possibilities for enrichment of rare ESC-derived HP/SCs. CI - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Kauts, Mari-Liis AU - Kauts ML AD - Erasmus Medical Center Stem Cell Institute, Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands; Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK. FAU - Rodriguez-Seoane, Carmen AU - Rodriguez-Seoane C AD - Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK. FAU - Kaimakis, Polynikis AU - Kaimakis P AD - Erasmus Medical Center Stem Cell Institute, Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands. FAU - Mendes, Sandra C AU - Mendes SC AD - Erasmus Medical Center Stem Cell Institute, Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands. FAU - Cortes-Lavaud, Xabier AU - Cortes-Lavaud X AD - Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK. FAU - Hill, Undine AU - Hill U AD - Erasmus Medical Center Stem Cell Institute, Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands. FAU - Dzierzak, Elaine AU - Dzierzak E AD - Erasmus Medical Center Stem Cell Institute, Department of Cell Biology, Erasmus Medical Center, Rotterdam, the Netherlands; Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK. Electronic address: elaine.dzierzak@ed.ac.uk. LA - eng GR - R37 DK054077/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20171221 PL - United States TA - Stem Cell Reports JT - Stem cell reports JID - 101611300 RN - 0 (Antigens, Ly) RN - 0 (GATA2 Transcription Factor) RN - 0 (Gata2 protein, mouse) RN - 0 (Ly6a protein, mouse) RN - 0 (Membrane Proteins) SB - IM MH - Animals MH - Antigens, Ly/genetics/metabolism MH - *Cell Differentiation MH - *GATA2 Transcription Factor/genetics/metabolism MH - *Genes, Reporter MH - Hematopoietic Stem Cells/cytology/*metabolism MH - Membrane Proteins/genetics/metabolism MH - Mice MH - Mouse Embryonic Stem Cells/cytology/*metabolism PMC - PMC5768964 OTO - NOTNLM OT - AGM OT - EMP OT - Gata2 OT - Gata2Venus OT - Ly6a(SCA1) OT - Ly6a(SCA1)GFP OT - double reporter ESC OT - embryonic stem cells OT - hematopoiesis OT - hematopoietic differentiation EDAT- 2017/12/26 06:00 MHDA- 2018/12/27 06:00 PMCR- 2017/12/21 CRDT- 2017/12/26 06:00 PHST- 2016/12/18 00:00 [received] PHST- 2017/11/24 00:00 [revised] PHST- 2017/11/27 00:00 [accepted] PHST- 2017/12/26 06:00 [pubmed] PHST- 2018/12/27 06:00 [medline] PHST- 2017/12/26 06:00 [entrez] PHST- 2017/12/21 00:00 [pmc-release] AID - S2213-6711(17)30526-X [pii] AID - 10.1016/j.stemcr.2017.11.018 [doi] PST - ppublish SO - Stem Cell Reports. 2018 Jan 9;10(1):151-165. doi: 10.1016/j.stemcr.2017.11.018. Epub 2017 Dec 21.