Distinct routes of lineage development reshape the human blood hierarchy across ontogeny
Open accessAbstract
Adjusting hematopoietic hierarchy: In adults, more than 300 billion blood cells are replenished daily. This output arises from a cellular hierarchy where stem cells differentiate into a series of multilineage progenitors, culminating in unilineage progenitors that generate over 10 different mature blood cell types. Notta et al. mapped the lineage potential of nearly 3000 single cells from 33 different cell populations of stem and progenitor cells from fetal liver, cord blood, and adult bone marrow (see the Perspective by Cabezas-Wallscheid and Trumpp). Prenatally, stem cell and progenitor populations were multilineage with few unilineage progenitors. In adults, multilineage cell potential was only seen in stem cell populations. Science , this issue p. 10.1126/science.aab2116 ; see also p. 126
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Recent scSeq state maps, barcode-based clonal studies, and single-cell culture work indicate that traditional intermediate cell types are internally heterogeneous in state and fate potential, with HSPCs on a continuum rather than a stepwise hierarchy.
“But recent state maps from scSeq (9), as well as clonal studies using barcodes (10) and single cell culture (11), suggest that the traditional intermediate cell types are internally heterogeneous in state and fate potential, with HSPCs lying along a continuum of states rather than a stepwise hierarchy.”
From Lineage tracing on transcriptional landscapes links state to fate during differentiation (2020) · cites this paper as [11]
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Experimental — accuracy not yet measuredM131I is predicted to impact protein structure.
“M131I, predicted to impact protein structure 61”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [61]
The Discussion passage concerns molecular markers of blood-cell lineage differentiation, not the M131I variant or its effect on protein structure. Searches for “M131I” and protein-structure predictions found no passage addressing the claim in our copy. (LLM, conf=0.75)
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- Authors
- Notta, F., Zandi, S., Takayama, N., Dobson, S., Gan, O. I., Wilson, G., Kaufmann, K. B., McLeod, J., Laurenti, E., Dunant, C. F., McPherson, J. D., Stein, L. D., Dror, Y., & Dick, J. E.
- Affiliations
- University Health Network (CA)
- Ontario Institute for Cancer Research (CA)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- École Polytechnique Fédérale de Lausanne (CH)
- University of Toronto (CA)
- Corresponding author
- Notta, Faiyaz
- Zandi, Sasan
- Dick, John E.
- ORCID
- Venue
- Science
- Published
- 2016-01-08
- Volume
- 351
- Issue
- 6269
- Pages
- aab2116-aab2116
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4816201
- OpenAlex
- W2171172082
- Cited by
- 780
- References
- 45
- Citations by year
- 2026: 34 · 2025: 44 · 2024: 53 · 2023: 60 · 2022: 63 · 2021: 96 · 2020: 111 · 2019: 84 · 2018: 93 · 2017: 83 · 2016: 56 · 2015: 3
- FWCI
- 61.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Apollo (University of Cambridge) (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Cambridge University Engineering Department Publications Database (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Canadian Institute of Health Research (CIHR)
- Aplastic Anemia and Myelodysplasia Association of Canada
- Ontario Institute of Cancer Research (OICR)
- Ontario Ministry of Research and Innovation
- Wellcome Trust
- Canadian Cancer Society
- Terry Fox Foundation
- Ontario Genomics Institute
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- hematopoiesis, multipotent stem cells, myeloid lineage, erythroid lineage, megakaryocytic lineage, fetal liver, adult bone marrow, human ontogeny, CD34+ cells, cell sorting
- MeSH terms
- Adult, Cell Separation, Cells, Cultured, Fetal Blood, Hematopoiesis, Humans, Liver, Megakaryocytes, Transcription, Genetic, Antigens, CD34, Cell Lineage, Gene Expression Profiling, Myeloid Cells, Multipotent Stem Cells, Erythroid Cells, Megakaryocyte Progenitor Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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