Decoding human fetal liver haematopoiesis
Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Research
2019
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| _version_ | 1797054782535368704 |
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| author | Popescu, D Botting, R Stephenson, E Roy, A al., E |
| author_facet | Popescu, D Botting, R Stephenson, E Roy, A al., E |
| author_sort | Popescu, D |
| collection | OXFORD |
| description | Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs. |
| first_indexed | 2024-03-06T19:02:05Z |
| format | Journal article |
| id | oxford-uuid:13e16c1a-688d-4df6-b44a-f616ea69f2c3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:02:05Z |
| publishDate | 2019 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:13e16c1a-688d-4df6-b44a-f616ea69f2c32022-03-26T10:16:25ZDecoding human fetal liver haematopoiesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:13e16c1a-688d-4df6-b44a-f616ea69f2c3EnglishSymplectic Elements at OxfordNature Research2019Popescu, DBotting, RStephenson, ERoy, Aal., EDefinitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs. |
| spellingShingle | Popescu, D Botting, R Stephenson, E Roy, A al., E Decoding human fetal liver haematopoiesis |
| title | Decoding human fetal liver haematopoiesis |
| title_full | Decoding human fetal liver haematopoiesis |
| title_fullStr | Decoding human fetal liver haematopoiesis |
| title_full_unstemmed | Decoding human fetal liver haematopoiesis |
| title_short | Decoding human fetal liver haematopoiesis |
| title_sort | decoding human fetal liver haematopoiesis |
| work_keys_str_mv | AT popescud decodinghumanfetalliverhaematopoiesis AT bottingr decodinghumanfetalliverhaematopoiesis AT stephensone decodinghumanfetalliverhaematopoiesis AT roya decodinghumanfetalliverhaematopoiesis AT ale decodinghumanfetalliverhaematopoiesis |