PMID- 30084753
OWN - NLM
STAT- MEDLINE
DCOM- 20190930
LR  - 20190930
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Print)
IS  - 1547-3287 (Linking)
VI  - 27
IP  - 21
DP  - 2018 Nov 1
TI  - TGFBI Expressed by Bone Marrow Niche Cells and Hematopoietic Stem and Progenitor 
      Cells Regulates Hematopoiesis.
PG  - 1494-1506
LID - 10.1089/scd.2018.0124 [doi]
AB  - The interactions of hematopoietic stem and progenitor cells (HSPCs) with 
      extracellular matrix (ECM) components and cells from the bone marrow (BM) 
      microenvironment control their homeostasis. Regenerative BM conditions can induce 
      expression of the ECM protein transforming growth factor beta-induced gene H3 
      (TGFBI or BIGH3) in murine HSPCs. In this study, we examined how increased or 
      reduced TGFBI expression in human HSPCs and BM mesenchymal stromal cells (MSCs) 
      affects HSPC maintenance, differentiation, and migration. HSPCs that 
      overexpressed TGFBI showed accelerated megakaryopoiesis, whereas granulocyte 
      differentiation and proliferation of granulocyte, erythrocyte, and monocyte 
      cultures were reduced. In addition, both upregulation and downregulation of TGFBI 
      expression impaired HSPC colony-forming capacity of HSPCs. Interestingly, the 
      colony-forming capacity of HSPCs with reduced TGFBI levels was increased after 
      long-term co-culture with MSCs, as measured by long-term culture-colony forming 
      cell (LTC-CFC) formation. Moreover, TGFBI downregulation in HSPCs resulted in 
      increased cobblestone area-forming cell (CAFC) frequency, a measure for 
      hematopoietic stem cell (HSC) capacity. Concordantly, TGFBI upregulation in HSPCs 
      resulted in a decrease of CAFC and LTC-CFC frequency. These results indicate that 
      reduced TGFBI levels in HSPCs enhanced HSC maintenance, but only in the presence 
      of MSCs. In addition, reduced levels of TGFBI in MSCs affected MSC/HSPC 
      interaction, as observed by an increased migration of HSPCs under the stromal 
      layer. In conclusion, tight regulation of TGFBI expression in the BM niche is 
      essential for balanced HSPC proliferation and differentiation.
FAU - Klamer, Sofieke E
AU  - Klamer SE
AD  - 1 Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, 
      Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
FAU - Dorland, Yvonne L
AU  - Dorland YL
AD  - 2 Sanquin Research and Landsteiner Laboratory, Department of Molecular and 
      Cellular Hemostasis, Academic Medical Center, University of Amsterdam , 
      Amsterdam, the Netherlands .
FAU - Kleijer, Marion
AU  - Kleijer M
AD  - 1 Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, 
      Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
FAU - Geerts, Dirk
AU  - Geerts D
AD  - 3 Department of Medical Biology, Academic Medical Center, University of Amsterdam 
      , Amsterdam, the Netherlands .
FAU - Lento, William E
AU  - Lento WE
AD  - 4 Department of Pharmacology, Duke University , Durham, North Carolina.
FAU - van der Schoot, C Ellen
AU  - van der Schoot CE
AD  - 5 Sanquin Research and Landsteiner Laboratory, Department of Experimental 
      Immunohematology, Academic Medical Center, University of Amsterdam , Amsterdam, 
      the Netherlands .
AD  - 6 Department of Hematology, Academic Medical Center , Amsterdam, the Netherlands 
      .
FAU - von Lindern, Marieke
AU  - von Lindern M
AD  - 1 Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, 
      Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
FAU - Voermans, Carlijn
AU  - Voermans C
AD  - 1 Sanquin Research and Landsteiner Laboratory, Department of Hematopoiesis, 
      Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
LA  - eng
PT  - Journal Article
DEP - 20180906
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 148710-76-3 (betaIG-H3 protein)
SB  - IM
MH  - Bone Marrow Cells/cytology
MH  - Cell Differentiation/genetics
MH  - Cell Line
MH  - Cell Movement/genetics
MH  - Cell Proliferation/*genetics
MH  - Cobblestone Lissencephaly/genetics
MH  - Coculture Techniques
MH  - Extracellular Matrix Proteins/*genetics
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Developmental
MH  - Genetic Vectors
MH  - Hematopoiesis/genetics
MH  - Hematopoietic Stem Cells/*cytology/metabolism
MH  - Humans
MH  - Lentivirus/genetics
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Stem Cells/*cytology/metabolism
MH  - Transforming Growth Factor beta/*genetics
PMC - PMC6209430
OTO - NOTNLM
OT  - CAFC
OT  - ECM
OT  - LTC-CFC
OT  - TGFBI
OT  - lineage differentiation
OT  - migration
COIS- No competing financial interests exist.
EDAT- 2018/08/08 06:00
MHDA- 2019/10/01 06:00
PMCR- 2018/10/25
CRDT- 2018/08/08 06:00
PHST- 2018/08/08 06:00 [pubmed]
PHST- 2019/10/01 06:00 [medline]
PHST- 2018/08/08 06:00 [entrez]
PHST- 2018/10/25 00:00 [pmc-release]
AID - 10.1089/scd.2018.0124 [pii]
AID - 10.1089/scd.2018.0124 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2018 Nov 1;27(21):1494-1506. doi: 10.1089/scd.2018.0124. Epub 
      2018 Sep 6.