scholarly journals 3D Microenvironment-Specific Mechanosensing Regulates Neural Stem Cell Lineage Commitment

2021 ◽  
Author(s):  
Jieung Baek ◽  
Paola A Lopez ◽  
Sangmin Lee ◽  
Taek-Soo Kim ◽  
Sanjay Kumar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Cell Lineage ◽  
Lineage Commitment ◽  
Confining Stress ◽  
Volumetric Growth ◽  
3D Microenvironment ◽  
Cell Commitment

While extracellular matrix (ECM) mechanics strongly regulate stem cell commitment, the field′s mechanistic understanding of this phenomenon largely derives from simplified two–dimensional (2D) culture substrates. Here we found a three-dimensional (3D) matrix–specific mechanoresponsive mechanism for neural stem cell (NSC) differentiation. NSC lineage commitment in 3D is maximally stiffness-sensitive in the range of 0.1–1.2 kPa, a narrower and more brain-mimetic range than we had previously identified in 2D (0.75–75 kPa). Transcriptomics revealed stiffness-dependent upregulation of early growth response 1 (Egr1) in 3D but not in 2D. Egr1 knockdown enhanced neurogenesis in stiff ECMs by driving β–catenin nuclear localization and activity in 3D, but not in 2D. Mechanical modeling and experimental studies under osmotic pressure indicate that stiff 3D ECMs are likely to stimulate Egr1 via increases in confining stress during cell volumetric growth. To our knowledge, Egr1 represents the first 3D–specific stem cell mechanoregulatory factor.

mSEL-1L deficiency affects vasculogenesis and neural stem cell lineage commitment

2017 ◽  
Vol 233 (4) ◽  
pp. 3152-3163 ◽  
Author(s):  
Marina Cardano ◽  
Giuseppe R. Diaferia ◽  
Luciano Conti ◽  
Simona Baronchelli ◽  
Alessandro Sessa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Cell Lineage ◽  
Lineage Commitment ◽  
Stem Cell Lineage

scholarly journals Organizational metrics of interchromatin speckle factor domains: integrative classifier for stem cell adhesion & lineage signaling

2015 ◽  
Vol 7 (4) ◽  
pp. 435-446 ◽  
Author(s):  
Sebastián L. Vega ◽  
Anandika Dhaliwal ◽  
Varun Arvind ◽  
Parth J. Patel ◽  
Nick R. M. Beijer ◽  
...  
Keyword(s):  
Content Analysis ◽  
Stem Cell ◽  
Cell Adhesion ◽  
Nuclear Protein ◽  
Cell Lineage ◽  
Lineage Commitment ◽  
Cell Microenvironment ◽  
Stem Cell Lineage ◽  
High Content Analysis

Timely classification of stem cell lineage commitment in response to cell–microenvironment interactions using high content analysis of sub-nuclear protein organization.

scholarly journals T-cell lineage commitment and cytokine responses of thymic progenitors

Blood ◽  
1995 ◽  
Vol 86 (5) ◽  
pp. 1850-1860 ◽  
Author(s):  
TA Moore ◽  
A Zlotnik
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Function ◽  
Cultured Cells ◽  
Critical Role ◽  
Cell Lineage ◽  
Lineage Commitment ◽  
Organ Cultures ◽  
Cell Commitment

The earliest steps of intrathymic differentiation recently have been elucidated. It has been reported that both CD4lo (CD44+ CD25- c-kit+ CD3- CD4lo CD8-) and pro-T cells (CD44+ CD25+ c-kit+ CD3- CD4- CD8-, representing the next step in maturation) exhibit germline T-cell receptor beta and gamma loci, suggesting that neither population is exclusively committed to the T-cell lineage. Several groups have shown that CD4lo cells retain the capacity to generate multiple lymphoid lineages in vivo; however, the lineage commitment status of pro-T cells is unknown. To determine when T-cell lineage commitment occurs, we examined the ability of sorted CD4lo and pro-T cells to generate lymphoid lineage cells in vivo or in fetal thymic organ cultures (FTOCs). When intravenously injected into scid mice, CD4lo cells generated both T and B cells, whereas the progeny of pro-T cells contained T cells exclusively. Fetal thymic organ cultures repopulated with CD4lo cells contained both T and natural killer (NK) cells, whereas cultures repopulated with pro-T cells contained T cells almost exclusively. These observations strongly suggest that T-cell lineage commitment occurs during the transition of CD4lo to pro-T cells. Because it is likely that the thymic microenvironment plays a critical role in T-cell commitment, we compared the responses of CD4lo and pro-T cells to various cytokine combinations in vitro, as well as the ability of the cultured cells to repopulate organ cultures. Cytokine combinations that maintained T-cell repopulation potential for both CD4lo and pro-T cells were found. CD4lo cells proliferated best in response to the combination containing interleukin-1 (IL-1), IL-3, IL- 6, IL-7, and stem cell factor (SCF). Unlike CD4lo cells, pro-T cells were much more dependent upon IL-7 for proliferation and FTOC repopulation. However, combinations of cytokines lacking IL-7 were found that maintained the T-cell repopulating potential of pro-T cells, suggesting that, whereas this cytokine is clearly very important for normal pro-T cell function, it is not an absolute necessity during early T-cell expansion and differentiation.

scholarly journals GEF-H1 controls focal adhesion signaling that regulates mesenchymal stem cell lineage commitment

Development ◽  
2014 ◽  
Vol 141 (20) ◽  
pp. e2005-e2005
Author(s):  
I.-H. Huang ◽  
C.-T. Hsiao ◽  
J.-C. Wu ◽  
R.-F. Shen ◽  
C.-Y. Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Focal Adhesion ◽  
Cell Lineage ◽  
Lineage Commitment ◽  
Stem Cell Lineage

scholarly journals Methyl-CpG-Binding Protein MBD1 Regulates Neuronal Lineage Commitment through Maintaining Adult Neural Stem Cell Identity

2016 ◽  
Vol 37 (3) ◽  
pp. 523-536 ◽  
Author(s):  
Emily M. Jobe ◽  
Yu Gao ◽  
Brian E. Eisinger ◽  
Janessa K. Mladucky ◽  
Charles C. Giuliani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Binding Protein ◽  
Lineage Commitment ◽  
Cell Identity ◽  
Adult Neural Stem Cell ◽  
Neuronal Lineage
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