PMID- 33418191
OWN - NLM
STAT- MEDLINE
DCOM- 20210528
LR  - 20210528
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 539
DP  - 2021 Feb 5
TI  - Hoxb5 defines the heterogeneity of self-renewal capacity in the hematopoietic 
      stem cell compartment.
PG  - 34-41
LID - S0006-291X(20)32260-9 [pii]
LID - 10.1016/j.bbrc.2020.12.077 [doi]
AB  - Self-renewal and multipotency are essential functions of hematopoietic stem cells 
      (HSCs). To maintain homeostatic hematopoiesis, functionally uniform HSCs have 
      been thought to be an ideal cell-of-origin. Recent technological advances in the 
      field have allowed us to analyze HSCs with single cell resolution and implicate 
      that functional heterogeneity may exist even within the highly purified HSC 
      compartment. However, due in part to the technical limitations of analyzing 
      extremely rare populations and our incomplete understanding of HSC biology, 
      neither the biological meaning of why heterogeneity exists nor the precise 
      mechanism of how heterogeneity is determined within the HSC compartment is 
      entirely known. Here we show the first evidence that self-renewal capacity varies 
      with the degree of replication stress dose and results in heterogeneity within 
      the HSC compartment. Using the Hoxb5-reporter mouse line which enables us to 
      distinguish between long-term (LT)-HSCs and short-term (ST)-HSCs, we have found 
      that ST-HSCs quickly lose self-renewal capacity under high stress environments 
      but can maintain self-renewal under low stress environments for long periods of 
      time. Critically, exogeneous Hoxb5 expression confers protection against loss of 
      self-renewal to Hoxb5-negative HSCs and can partially alter the cell fate of 
      ST-HSCs to that of LT-HSCs. Our results demonstrate that Hoxb5 imparts functional 
      heterogeneity in the HSC compartment by regulating self-renewal capacity. 
      Additionally, Hoxb5-positive HSCs may exist as fail-safe system to protect from 
      the exhaustion of HSCs throughout an organism's lifespan.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Sakamaki, Taro
AU  - Sakamaki T
AD  - RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, 650-0047, 
      Japan; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto 
      University, Kyoto, Kyoto, 606-8397, Japan.
FAU - Kao, Kevin S
AU  - Kao KS
AD  - Weill Cornell, Rockefeller, Sloan Kettering Tri-Institutional MD-PhD Program, New 
      York, NY, 10065, USA.
FAU - Nishi, Katsuyuki
AU  - Nishi K
AD  - RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, 650-0047, 
      Japan; Department of Hematology and Oncology, Graduate School of Medicine, Kyoto 
      University, Kyoto, Kyoto, 606-8397, Japan.
FAU - Chen, James Y
AU  - Chen JY
AD  - Massachusetts General Hospital, Department of Medicine, Harvard Medical School, 
      Boston, MA, 02114, USA.
FAU - Sadaoka, Kay
AU  - Sadaoka K
AD  - RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, 650-0047, 
      Japan.
FAU - Fujii, Momo
AU  - Fujii M
AD  - RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, 650-0047, 
      Japan.
FAU - Takaori-Kondo, Akifumi
AU  - Takaori-Kondo A
AD  - Department of Hematology and Oncology, Graduate School of Medicine, Kyoto 
      University, Kyoto, Kyoto, 606-8397, Japan.
FAU - Weissman, Irving L
AU  - Weissman IL
AD  - Institute for Stem Cell Biology and Regenerative Medicine and Ludwig Center for 
      Cancer Stem Cell Biology and Medicine, USA; Department of Pathology and 
      Developmental Biology, Stanford University School of Medicine, Stanford, CA, 
      94305, USA.
FAU - Miyanishi, Masanori
AU  - Miyanishi M
AD  - RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Hyogo, 650-0047, 
      Japan. Electronic address: masanori.miyanishi@riken.jp.
LA  - eng
PT  - Journal Article
DEP - 20210105
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Hoxb5 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/physiology
MH  - Cell Lineage
MH  - Cell Proliferation/physiology
MH  - Cell Self Renewal/physiology
MH  - Hematopoiesis
MH  - Hematopoietic Stem Cells/*cytology/*metabolism
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Mice
OTO - NOTNLM
OT  - Hematopoietic stem cell
OT  - Heterogeneity
OT  - Hoxb5
OT  - LT-HSC
OT  - ST-HSC
OT  - Self-renewal
COIS- Declaration of competing interest We have no competing interests to declare.
EDAT- 2021/01/09 06:00
MHDA- 2021/05/29 06:00
CRDT- 2021/01/08 20:14
PHST- 2020/12/13 00:00 [received]
PHST- 2020/12/19 00:00 [revised]
PHST- 2020/12/21 00:00 [accepted]
PHST- 2021/01/09 06:00 [pubmed]
PHST- 2021/05/29 06:00 [medline]
PHST- 2021/01/08 20:14 [entrez]
AID - S0006-291X(20)32260-9 [pii]
AID - 10.1016/j.bbrc.2020.12.077 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2021 Feb 5;539:34-41. doi: 
      10.1016/j.bbrc.2020.12.077. Epub 2021 Jan 5.