@article{0194d845235944899d03a683ab94e493,
title = "Definitive hematopoietic stem cells minimally contribute to embryonic hematopoiesis",
abstract = "Hematopoietic stem cells (HSCs) are rare cells that arise in the embryo and sustain adult hematopoiesis. Although the functional potential of nascent HSCs is detectable by transplantation, their native contribution during development is unknown, in part due to the overlapping genesis and marker gene expression with other embryonic blood progenitors. Using single-cell transcriptomics, we define gene signatures that distinguish nascent HSCs from embryonic blood progenitors. Applying a lineage-tracing approach to selectively track HSC output in situ, we find significantly delayed lymphomyeloid contribution. An inducible HSC injury model demonstrates a negligible impact on larval lymphomyelopoiesis following HSC depletion. HSCs are not merely dormant at this developmental stage, as they showed robust regeneration after injury. Combined, our findings illuminate that nascent HSCs self-renew but display differentiation latency, while HSC-independent embryonic progenitors sustain developmental hematopoiesis. Understanding these differences could improve de novo generation and expansion of functional HSCs.",
keywords = "developmental hematopoiesis, differentiation, hematopoietic progenitors, hematopoietic stem cell, lineage tracing, scRNA-seq, self-renewal, zebrafish",
author = "Ulloa, {Bianca A.} and Habbsa, {Samima S.} and Potts, {Kathryn S.} and Alana Lewis and Mia McKinstry and Payne, {Sara G.} and Flores, {Julio C.} and Anastasia Nizhnik and {Feliz Norberto}, Maria and Christian Mosimann and Bowman, {Teresa V.}",
note = "Funding Information: This work was funded by the American Cancer Society (grant RSG-129527-DDC), the DOD (grant BM180109), the NIH (grant 1R01DK121738), and the Edward P. Evans Foundation (T.V.B.); the NIH (grants T32GM007288 and F31HL152562) (B.A.U.); the Einstein SOARS program (S.S.H.); the American Australian Association Sir Rupert Murdoch Postdoctoral Fellowship (K.S.P.); The Einstein Training Program in Stem Cell Research funded by the Empire State Stem Cell Fund through New York State Department of Health contract C30292GG (K.S.P. and A.N.); NIH F31HD097901 (S.G.P.); and funds from the University of Colorado School of Medicine and the Children's Hospital Colorado Foundation (C.M.). Instrumental feedback to the growth of this project was provided by Britta Will, Kira Gritsman, Ulrich Steidl, and Sofia De Oliveira. We would like to thank several Einstein Core Facilities supported by NIH grant P30CA013330, including Flow Cytometry, Genomics, and Computational Genomics Facilities. For their assistance with cell sorting and flow cytometry analysis, we thank the Flow Cytometry core members Jinghang Zhang, Yu (Joey) Zhang, Fnu (Aodeng) Aodengtuya, and Ming Liu. Additionally, we would like to thank the Einstein Genomics Core and David Reynolds for their assistance with 10X Genomics scRNA pre-processing and library preparation. For their computational support, thank you to Tobias Schraink, the Einstein Computational Genomics Core, and Dr. Robert Dubin. For their animal support, we thank the Einstein Zebrafish core members Clinton de Paolo and Spartak Kalinin. Lastly, we greatly thank the Hadland lab and its members, especially Dr. Brandon Hadland and Tessa Dignum, for their guidance with scRNA-seq analysis and providing code. Conceptualization, T.V.B. B.A.U. and S.S.H.; methodology, T.V.B. B.A.U. S.S.H. K.S.P. A.N. A.L. M.M. S.G.P. J.C.F. M.F.N. and C.M.; investigation, T.V.B. B.A.U. S.S.H. A.N. and J.C.F.; writing – original draft, T.V.B. B.A.U. and S.S.H.; writing – review & editing, T.V.B. B.A.U. K.S.P. and C.M.; funding acquisition, T.V.B. and B.A.U.; supervision, T.V.B. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. Funding Information: This work was funded by the American Cancer Society (grant RSG-129527-DDC ), the DOD (grant BM180109 ), the NIH (grant 1R01DK121738 ), and the Edward P. Evans Foundation (T.V.B.); the NIH (grants T32GM007288 and F31HL152562 ) (B.A.U.); the Einstein SOARS program (S.S.H.); the American Australian Association Sir Rupert Murdoch Postdoctoral Fellowship (K.S.P.); The Einstein Training Program in Stem Cell Research funded by the Empire State Stem Cell Fund through New York State Department of Health contract C30292GG (K.S.P. and A.N.); NIH F31HD097901 (S.G.P.); and funds from the University of Colorado School of Medicine and the Children{\textquoteright}s Hospital Colorado Foundation (C.M.). Instrumental feedback to the growth of this project was provided by Britta Will, Kira Gritsman, Ulrich Steidl, and Sofia De Oliveira. We would like to thank several Einstein Core Facilities supported by NIH grant P30CA013330 , including Flow Cytometry, Genomics, and Computational Genomics Facilities. For their assistance with cell sorting and flow cytometry analysis, we thank the Flow Cytometry core members Jinghang Zhang, Yu (Joey) Zhang, Fnu (Aodeng) Aodengtuya, and Ming Liu. Additionally, we would like to thank the Einstein Genomics Core and David Reynolds for their assistance with 10X Genomics scRNA pre-processing and library preparation. For their computational support, thank you to Tobias Schraink, the Einstein Computational Genomics Core, and Dr. Robert Dubin. For their animal support, we thank the Einstein Zebrafish core members Clinton de Paolo and Spartak Kalinin. Lastly, we greatly thank the Hadland lab and its members, especially Dr. Brandon Hadland and Tessa Dignum, for their guidance with scRNA-seq analysis and providing code. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = sep,
day = "14",
doi = "10.1016/j.celrep.2021.109703",
language = "English (US)",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",
}