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Single-cell multiomics of human fetal hematopoiesis define a developmental-specific population and a fetal signature

Sommarin, Mikael N.E. LU ; Olofzon, Rasmus LU orcid ; Palo, Sara LU ; Dhapola, Parashar LU ; Soneji, Shamit LU ; Karlsson, Göran LU and Böiers, Charlotta LU (2023) In Blood Advances 7(18). p.5325-5340
Abstract

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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood Advances
volume
7
issue
18
pages
16 pages
publisher
American Society of Hematology
external identifiers
  • pmid:37379274
  • scopus:85168301461
ISSN
2473-9529
DOI
10.1182/bloodadvances.2023009808
language
English
LU publication?
yes
id
ed86d789-f409-4c49-a6a6-2eb2d24773fa
date added to LUP
2024-01-12 14:29:12
date last changed
2024-10-27 03:42:51
@article{ed86d789-f409-4c49-a6a6-2eb2d24773fa,
  abstract     = {{<p>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.</p>}},
  author       = {{Sommarin, Mikael N.E. and Olofzon, Rasmus and Palo, Sara and Dhapola, Parashar and Soneji, Shamit and Karlsson, Göran and Böiers, Charlotta}},
  issn         = {{2473-9529}},
  language     = {{eng}},
  number       = {{18}},
  pages        = {{5325--5340}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood Advances}},
  title        = {{Single-cell multiomics of human fetal hematopoiesis define a developmental-specific population and a fetal signature}},
  url          = {{http://dx.doi.org/10.1182/bloodadvances.2023009808}},
  doi          = {{10.1182/bloodadvances.2023009808}},
  volume       = {{7}},
  year         = {{2023}},
}