Robust temporal map of human in vitro myelopoiesis using single-cell genomics
Alsinet, Clara (Open Targets. Wellcome Genome Campus)
Primo, Maria Nascimento (Open Targets. Wellcome Genome Campus)
Lorenzi, Valentina (Wellcome Sanger Institute. Wellcome Genome Campus)
Bello, Erica (Open Targets. Wellcome Genome Campus)
Kelava, Iva (Wellcome Sanger Institute. Wellcome Genome Campus)
Jones, Carla P. (Wellcome Sanger Institute. Wellcome Genome Campus)
Vilarrasa Blasi, Roser (Wellcome Sanger Institute. Wellcome Genome Campus)
Sancho Serra, Carmen (Wellcome Sanger Institute. Wellcome Genome Campus)
Knights, Andrew J. (Wellcome Sanger Institute. Wellcome Genome Campus)
Park, Jong Eun (Korea Advanced Institute of Science and Technology)
Wyspianska, Beata S. (Immunology Research Unit. Medicines Research Centre. GlaxoSmithKline)
Trynka, Gosia (Open Targets. Wellcome Genome Campus)
Tough, David F. (Immunology Research Unit. Medicines Research Centre. GlaxoSmithKline)
Bassett, Andrew (Open Targets. Wellcome Genome Campus)
Gaffney, Daniel J. (Wellcome Sanger Institute. Wellcome Genome Campus)
Álvarez-Errico, Damiana (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Vento Tormo, Roser (Wellcome Sanger Institute. Wellcome Genome Campus)

Fecha:	2022
Resumen:	Myeloid cells are central to homeostasis and immunity. Characterising in vitro myelopoiesis protocols is imperative for their use in research, immunotherapies, and understanding human myelopoiesis. Here, we generate a >470K cells molecular map of human induced pluripotent stem cells (iPSC) differentiation into macrophages. Integration with in vivo single-cell atlases shows in vitro differentiation recapitulates features of yolk sac hematopoiesis, before definitive hematopoietic stem cells (HSC) emerge. The diversity of myeloid cells generated, including mast cells and monocytes, suggests that HSC-independent hematopoiesis can produce multiple myeloid lineages. We uncover poorly described myeloid progenitors and conservation between in vivo and in vitro regulatory programs. Additionally, we develop a protocol to produce iPSC-derived dendritic cells (DC) resembling cDC2. Using CRISPR/Cas9 knock-outs, we validate the effects of key transcription factors in macrophage and DC ontogeny. This roadmap of myeloid differentiation is an important resource for investigating human fetal hematopoiesis and new therapeutic opportunities.
Nota:	We thank the Cellular Genetics wet lab support team, Cellular Genetics IT team, Sanger Sequencing operations and Sanger Cytometry Core facility for their essential help. We thank the Gene Editing team for providing iPSC knock-out lines. We would also like to thank Ruxandra Tesloianu and Luz Garcia-Alonso for their help setting up the scATAC-seq computational analysis. We thank Jana Eliasova for her help with figure design and Christina Usher and Aidan Maartens for their edits in the text. This work was mainly funded by the Open Targets consortium (OTAR026 and OTAR032 project) and the Wellcome Sanger core funding (WT206194) with additional support from Open Targets projects OTAR037, OTAR2065, OTAR2071. The authors are grateful to the funders for their support and additional care given to their members during the COVID-19 pandemic. D.A.-E. thanks CERCA Programme/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. This study makes use of cell lines and data generated by the HiPSci Consortium, funded by The Wellcome Trust and the MRC (Medical Research Council). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This publication is part of the Human Cell Atlas- www.humancellatlas.org/publications.
Nota:	We thank the Cellular Genetics wet lab support team, Cellular Genetics IT team, Sanger Sequencing operations and Sanger Cytometry Core facility for their essential help. We thank the Gene Editing team for providing iPSC knock-out lines. We would also like to thank Ruxandra Tesloianu and Luz Garcia-Alonso for their help setting up the scATAC-seq computational analysis. We thank Jana Eliasova for her help with figure design and Christina Usher and Aidan Maartens for their edits in the text. This work was mainly funded by the Open Targets consortium (OTAR026 and OTAR032 project) and the Wellcome Sanger core funding (WT206194) with additional support from Open Targets projects OTAR037, OTAR2065, OTAR2071. The authors are grateful to the funders for their support and additional care given to their members during the COVID-19 pandemic. D.A.-E. thanks CERCA Programme/Generalitat de Catalunya and the Josep Carreras Foundation for institutional support. This study makes use of cell lines and data generated by the HiPSci Consortium, funded by The Wellcome Trust and the MRC (Medical Research Council). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This publication is part of the Human Cell Atlas-www.humancellatlas.org/publications.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Cell Differentiation ; Cell Lineage ; Genomics ; Hematopoiesis ; Humans ; Induced Pluripotent Stem Cells ; Myelopoiesis
Publicado en:	Nature communications, Vol. 13 Núm. 1 (december 2022) , p. 2885, ISSN 2041-1723

DOI: 10.1038/s41467-022-30557-4
PMID: 35610203

17 p, 5.1 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
Artículos > Artículos de investigación
Artículos > Artículos publicados