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Single-cell multiomics of human fetal hematopoiesis define a developmental-specific population and a fetal signature
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- Sommarin, Mikael N.E. (författare)
- Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine
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- Olofzon, Rasmus (författare)
- Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Utvecklingshematopoes,Forskargrupper vid Lunds universitet,Utvecklingslymfopoes och leukemi,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Developmental Hematopoiesis,Lund University Research Groups,Developmental lymphopoiesis and leukemia
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- Palo, Sara (författare)
- Lund University,Lunds universitet,Molekylär neuromodulering,Forskargrupper vid Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Utvecklingslymfopoes och leukemi,Molecular Neuromodulation,Lund University Research Groups,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Developmental lymphopoiesis and leukemia
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- 2023
- 2023
- Engelska 16 s.
- Ingår i: Blood Advances. - 2473-9529. ; 7:18, s. 5325-5340
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Knowledge of human fetal blood development and how it differs from adult blood is highly relevant to our understanding of congenital blood and immune disorders and childhood leukemia, of which the latter can originate in utero. Blood formation occurs in waves that overlap in time and space, adding to heterogeneity, which necessitates single-cell approaches. Here, a combined single-cell immunophenotypic and transcriptional map of first trimester primitive blood development is presented. Using CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), the molecular profile of established immunophenotype-gated progenitors was analyzed in the fetal liver (FL). Classical markers for hematopoietic stem cells (HSCs), such as CD90 and CD49F, were largely preserved, whereas CD135 (FLT3) and CD123 (IL3R) had a ubiquitous expression pattern capturing heterogenous populations. Direct molecular comparison with an adult bone marrow data set revealed that the HSC state was less frequent in FL, whereas cells with a lymphomyeloid signature were more abundant. An erythromyeloid–primed multipotent progenitor cluster was identified, potentially representing a transient, fetal-specific population. Furthermore, differentially expressed genes between fetal and adult counterparts were specifically analyzed, and a fetal core signature was identified. The core gene set could separate subgroups of acute lymphoblastic leukemia by age, suggesting that a fetal program may be partially retained in specific subgroups of pediatric leukemia. Our detailed single-cell map presented herein emphasizes molecular and immunophenotypic differences between fetal and adult blood cells, which are of significance for future studies of pediatric leukemia and blood development in general.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
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- Sommarin, Mikael ...
- Olofzon, Rasmus
- Palo, Sara
- Dhapola, Parasha ...
- Soneji, Shamit
- Karlsson, Göran
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- Böiers, Charlott ...
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