@article{5822410cc4324fafbe8f26b22a071bcc,
title = "Single-Cell Analysis of Neonatal HSC Ontogeny Reveals Gradual and Uncoordinated Transcriptional Reprogramming that Begins before Birth",
abstract = "Fetal and adult hematopoietic stem cells (HSCs) have distinct proliferation rates, lineage biases, gene expression profiles, and gene dependencies. Although these differences are widely recognized, it is not clear how the transition from fetal to adult identity is coordinated. Here we show that murine HSCs and committed hematopoietic progenitor cells (HPCs) undergo a gradual, rather than precipitous, transition from fetal to adult transcriptional states. The transition begins prior to birth and is punctuated by a late prenatal spike in type I interferon signaling that promotes perinatal HPC expansion and sensitizes progenitors to the leukemogenic FLT3ITD mutation. Most other changes in gene expression and enhancer activation are imprecisely timed and poorly coordinated. Thus, heterochronic enhancer elements, and their associated transcripts, are activated independently of one another rather than as part of a robust network. This simplifies the regulatory programs that guide neonatal HSC/HPC ontogeny, but it creates heterogeneity within these populations.",
keywords = "HSC development, interferon, neonatal hematopoiesis, single cell RNA-seq",
author = "Yanan Li and Wenjun Kong and Wei Yang and Patel, {Riddhi M.} and Casey, {Emily B.} and Theresa Okeyo-Owuor and White, {J. Michael} and Porter, {Shaina N.} and Morris, {Samantha A.} and Magee, {Jeffrey A.}",
note = "Funding Information: This work was supported by grants to J.A.M. from the National Heart, Lung, and Blood Institute (NHLBI) ( R01 HL136504 and R01 HL152180 ), Alex{\textquoteright}s Lemonade Stand Foundation (“A” Award), Gabrielle's Angel Foundation , The V Foundation , the American Society of Hematology , and the Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital . It was also supported by grants to S.A.M. from the National Institute of General Medical Sciences (NIGMS) ( R01 GM126112 ), the Silicon Valley Community Foundation , and the Chan Zuckerberg Initiative (grant HCA2-A-1708-02799 ). S.A.M. is supported by an Allen Distinguished Investigator Award (through the Paul G. Allen Frontiers Group ), a Vallee Scholar Award, and a Sloan Research Fellowship. Funding Information: This work was supported by grants to J.A.M. from the National Heart, Lung, and Blood Institute (NHLBI) (R01 HL136504 and R01 HL152180), Alex's Lemonade Stand Foundation (?A? Award), Gabrielle's Angel Foundation, The V Foundation, the American Society of Hematology, and the Children's Discovery Institute of Washington University and St. Louis Children's Hospital. It was also supported by grants to S.A.M. from the National Institute of General Medical Sciences (NIGMS) (R01 GM126112), the Silicon Valley Community Foundation, and the Chan Zuckerberg Initiative (grant HCA2-A-1708-02799). S.A.M. is supported by an Allen Distinguished Investigator Award (through the Paul G. Allen Frontiers Group), a Vallee Scholar Award, and a Sloan Research Fellowship. J.A.M. and S.A.M. designed and oversaw all experiments, conducted experiments, interpreted data, and wrote the manuscript. Y.L. and W.K. conducted experiments, interpreted data, and wrote the manuscript. W.Y. analyzed data. R.M.P. E.B.C. T.O.-O. J.M.W. and S.N.P. performed experiments. All authors reviewed and edited the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = nov,
day = "5",
doi = "10.1016/j.stem.2020.08.001",
language = "English",
volume = "27",
pages = "732--747.e7",
journal = "Cell Stem Cell",
issn = "1934-5909",
number = "5",
}